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Background: Repeated cocaine administration changes histone acetylation and methylation on Lys residues and Deoxyribonucleic acid (DNA) within the nucleus accumbens (NAc). Recently Nestler’s group explored histone Arg (R) methylation in reward processing models. Damez- Werno et al. (2016) reported that during human investigations and animal self-administration experiments, the histone mark protein-R-methyltransferase-6 (PRMT6) and asymmetric dimethylation of R2 on histone H3 (H3R2me2a) decreased in the rodent and cocaine-dependent human NAc. Overexpression of PRMT6 in D2-MSNs in all NAc neurons increased cocaine seeking, whereas PRMT6 overexpression in D1-MSNs protects against cocaine-seeking. Hypothesis: The hypothesis is that dopaminylation (H3R2me2a binding) occurs in psychostimulant use disorder (PSU), and the binding inhibitor Srcin1, like the major DRD2 A2 allelic polymorphism, protects against psychostimulant seeking behavior by normalizing nucleus accumbens (NAc) dopamine expression. Discussion: Numerous publications confirmed the association between the DRD2 Taq A1 allele (30-40 lower D2 receptor numbers) and severe cocaine dependence. Lepack et al. (2020) found that acute cocaine increases dopamine in NAc synapses, and results in histone H3 glutamine 5 dopaminylation (H3Q5dop) and consequent inhibition of D2 expression. The inhibition increases with chronic cocaine use and accompanies cocaine withdrawal. They also found that the Src kinase signaling inhibitor 1 (Srcin1 or p140CAP) during cocaine withdrawal reduced H3R2me2a binding. Consequently, this inhibited dopaminylation induced a “homeostatic brake.” Conclusion: The decrease in Src signaling in NAc D2-MSNs, (like the DRD2 Taq A2 allele, a well- known genetic mechanism protective against SUD) normalizes the NAc dopamine expression and decreases cocaine reward and motivation to self-administer cocaine. The Srcin1 may be an important therapeutic target.

Medicinal Plants are valuable source of phytochemicals which have been used in the medicine as source of raw material since very ancient time in the world. Flavonoids are one of the important classes of phytochemical basically present in the fruits, vegetables, grains, wine, tea etc. Flavonoids also play an important role in the defense mechanism of plants and produce different colours in the plants. Pectolinarigenin is a natural flavonoidal compound having molecular formula C17H14O6 and molecular weight 314.28. Pectolinarigenin is present in various plants and examples are Clerodendrum phlomidis, Eupatorium odoratum, Cirsium chanroenicum, Cirsium japonlcum, Chromolaena odorata, Cirsium setidens, and Trollius chinensis. Pectolinarigenin acts as an anticancer agent against various types of human malignancies, such as lung cancer, melanoma, hepatocellular carcinoma and colorectal adenocarcinoma. It has also anti-inflammatory, anti-allergy, cytotoxic and hepatoprotective properties. Pectolinarigenin gained attention from researchers and clinicians due to their anticancer properties and in future it could be the best choice for cancer treatment. The purpose of this review paper is to summarize all the pharmacological properties of pectolinarigenin on cancer and other disorders, describe the mode of action and possible pathways for cellular level action. The present review initially highlights the current status of flavonoids and their pharmaceutical importance, role of pectolinarigenin in human disorders, and in later section, summarizes analytical techniques of pectolinarigenin as lead molecules. This review will support all the ongoing research of pectolinarigenin through out world for their beneficial properties in all the scientific discipline.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

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Background Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy. Methods The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9–10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5–9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect. Discussion The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery. Trial registration ClinicalTrials.gov (identifier: NCT03369210). Electronic supplementary material The online version of this article (10.1186/s13063-019-3200-3) contains supplementary material, which is available to authorized users.

Pocas personas tienen la oportunidad de influir sobre el diseño de la vivienda donde van a habitar. Si esta oportunidad se les diera, muy pocos de ellos elegirían como modelo para su nueva vivienda un edificio de los años 60, alto y con una elevada densidad de apartamentos. Y si lo hicieran, no cabría esperar que los profesionales de la arquitectura les felicitaran por ello.Sin embargo, esto es exactamente lo que ha ocurrido con las viviendas Hulme en Manchester, en donde se ha erigido un edificio de buena construcción y bajo coste de mantenimiento sobre los escombros de uno de los peores ejemplos de construcción de viviendas de la postguerra. Estructuras de acero galvanizado ligeras, abiertas, han reemplazado a oscuros pasillos y escaleras de hormigón.

One of the significant advances in economic theory has been the incorporation of uncertainty into the models used to investigate economic behavior. The explicit treatment of uncertainty has permitted economists to predict the behavior of economic agents operating in an uncertain environment and to explain, for example, the existence of insurance, stock markets, and forward exchange markets that have no necessary role in a deterministic world. One natural application of the economics of uncertainty has been to the study of international trade and exchange in which uncertainty regarding exchange rates and relative prices is a prominent feature of the environment of economic agents. The purpose of this paper is to frame the international trade results developed in the recent works of Wolfgang Mayer and Raveendra Batra in light of the current state of the theory of the firm under uncertainty. Before analyzing the effect of uncertainty on international trade, a perspective on the application of the economics of uncertainty to neoclassical theory will be presented with an emphasis on the theory of the firm.