Cannabinoids help to unravel etiological aspects in common and bring hope for the treatment of autism and epilepsy

Desde 1843 que as propriedades anticonvulsivantes da Cannabis são conhecidas pela ciência ocidental. Em 1980, ensaios clínicos demonstraram que canabidiol possui atividade antiepilética em pacientes de epilepsia refratária, sendo sonolência o único efeito colateral. O embargo imposto pela proibição do uso medicinal da Cannabis, no entanto, prejudicou imensamente o desenvolvimento científico e a exploração dessas propriedades. Multiplicam-se, contudo, os casos bem sucedidos de uso ilegal e sem orientação para o tratamento de síndromes caracterizadas por epilepsia e autismo regressivo. Os resultados corroboram evidências científicas que indicam a existência de processos etiológicos comuns entre o autismo e a epilepsia. Estudos em modelos animais confirmam envolvimento do sistema endocanabinoide. Esses avanços apontam o início de uma revolução no entendimento e tratamento desses transtornos.Since 1843 the anticonvulsant properties of Cannabis are known by the Western science. In 1980, clinical trials have shown that cannabidiol has antiepileptic activity in refractory epilepsy patients, with drowsiness as the only side effect. The embargo imposed by banning medicinal Cannabis use, however, harmed scientific development and the exploration of these properties. However, there is a growing number of successful cases of illegal use without guidance for the treatment of syndromes characterized by epilepsy and regressive autism. The results corroborate scientific evidence that indicates the existence of common etiological aspects between autism and epilepsy. Studies in animal models have confirmed involvement of the endocannabinoid system. These advances indicate the beginning of a revolution in the understanding and treatment of these disorders

Constructing a Tough Shield around the Wellbore by Stabilizing the Multi-Scale Structure of Granular Plugging Zone in Deep Fractured Reservoirs

Fracture plugging zone with low strength is one of the key reasons for plugging failure in deep fractured reservoirs. Forming a high-strength plugging zone is a key engineering problem to be solved in wellbore strengthening. In this chapter, wellbore strengthening mechanisms of plugging zone for wellbore strengthening in deep fractured reservoirs are revealed from a relationship between mechanical structure and strength standpoint. Physical granular bridging materials dislocation and crushing under pressure fluctuation induce the strong force chains network failure, which leads to macroscale friction or shear failure of plugging zone. The main methods to improve microscale materials stability are to increase friction resistance, exert embedding effect, and strengthen bonding effect. Factors, which strengthen the meso-structure stability, include increasing shear strength and proportion of strong force chains. Key measures to strengthen the macrostructure stability of plugging zone are by improving its compactness, controlling its length, and ensuring the stability timeliness

Altered Tyrosine Phosphorylation of Cardiac Proteins Prompts Contractile Dysfunction in Hypertrophic Cardiomyopathy

Altered Serine/Threonine phosphorylation of the cardiac proteome is an established hallmark of heart failure (HF). However, the contribution of tyrosine phosphorylation to the pathogenesis of these diseases remains unclear. The cardiac proteome was explored by global mapping to discover and quantify site-specific tyrosine phosphorylation in two cardiac hypertrophic models; cardiac overexpression of ErbB2 (TgErbB2) and cardiac expression of a-Myosin heavy chain R403Q (R403Q-aMyHCTg) compared to control hearts. Phosphoproteomic changes found in R403Q-aMyHC Tg mice indicated EGFR1, Focal Adhesion, VEGF, ErbB signaling, and Chemokine signaling pathways activity were likely to be activated. On the other hand, TgErbB2 mice findings displayed significant overrepresentation of Right Ventricular Cardiomyopathy, Hypertrophic Cardiomyopathy (HCM), and dilated cardiomyopathy (DCM) KEGG Pathways. In silico kinase-substrate enrichment analysis (KSEA) highlighted a marked downregulation of canonical MAPK Pathway Activity downstream of k-Ras in TgErbB2 mice and activation of EGFR, PP2 inhibition of c-Src, and Hepatocyte growth factor stimulation. In vivo ErbB2 inhibition by AG-825 decreased cardiac fibrosis, cardiomyocyte disarray, and rescued contractile function on TgErbB2 mice. These results suggest that altered tyrosine phosphorylation may play a regulatory role in cardiac hypertrophic models, suggesting that tyrosine kinase inhibitors could be used therapeutically in Hypertrophic Cardiomyopathy

Effect of optimized thrombus aspiration on myocardial perfusion and prognosis in acute ST-segment elevation myocardial infarction patients with primary percutaneous coronary intervention

ObjectiveTo investigate the impact of optimized thrombus aspiration on myocardial perfusion, prognosis, and safety in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention(primary PCI).MethodsA total of 129 patients with STEMI were randomly allocated into control group (Subgroup A and B) and experimental group(Subgroup C and D). Control group received percutaneous transluminal coronary angioplasty (PTCA),thrombus aspiration and primary PCI. Experimental group received optimized thrombus aspiration and primary PCI. The number of thrombus aspiration was less than 4 times in Subgroup A and C. The number of thrombus aspiration was performed more than 4 times in Subgroups B and D. The classification of thrombi extracted, the TIMI flow grade, the incidence of no-reflow and slow flow, cTFC, TPI and CK-MB at 12 h and 24 h after stenting, ST segment resolution of ECG after stenting, NT-proBNP, LVEFat 24 h, 30 days and 180 days after stenting were compared between groups. The incidence of intraoperative and postoperative bleeding complications, stroke events and major cardiovascular events (MACE) were recorded and compared between groups.ResultsThe classification of thrombi extracted in the experimental group was higher than that in the control group. The TIMI flow grade of the experimental group was better than the control group after thrombus aspiration. After stenting, the advantage still existed, but the difference was not statistically significant. On cTFC, the experimental group was lower than the control group, but the difference was not statistically significant; After stenting the experimental group was significantly lower than the control group. The CK-MB at 12 h and 24 h of the experimental group was lower than the control group. After thrombus aspiration the incidence of no-reflow in the experimental group was significantly lower than that in the control group; after stenting the incidence of no-reflow in the experimental group was still lower than the control group, but no statistically difference. After thrombus aspiration and stenting the incidence of slow flow in the experimental group were lower than that in the control group. After stenting, NT-proBNP at 24 h was lower in the experimental group than that in the control group, However, there was no statistical difference; after stenting, The NT-proBNP in the experimental group was lower than that in the control group at 30 days and 180 days. After stenting, LVEF of the experimental group was significantly higher than the control group at 24 h and 30 days; superiority remained after 180 days but no statistical difference. There was no statistical difference between two groups for intraoperative and postoperative bleeding complications, stroke events, and MACE events. In Subgroup analysis,there was no significant difference in the classification of thrombi extracted, TIMI flow grade, cTFC, CK-MB,NT-proBNP and LVEF between group C and D, but group A was better than group B. Analysis of variance showed that the optimal number of suction was 4–5 times.ConclusionsOptimized thrombus aspiration can significantly improve myocardial perfusion and short-term and medium-term prognosis of STEMI patients after PCI, and reduce the incidence of slow flow and no-reflow. The optimal suction times were 4–5 times. Traditional aspiration method with more aspiration times is harmful to cardiac prognosis. Thrombus aspiration does not increase the incidence of stroke events and is safe.Clinical Trial Registration: identifier, ChiCTR2300073410

Using a Relative Quantitative Proteomic Method to Identify Differentially Abundant Proteins in Brucella melitensis Biovar 3 and Brucella melitensis M5-90

Brucellosis, caused by Brucella spp., is one of the most widespread bacterial zoonoses worldwide. Vaccination is still considered the best way to control brucellosis. An investigation into the differential proteome expression patterns of wild and vaccine strains may help researchers and clinicians differentiate between the strains to diagnose and better understand the mechanism(s) underlying differences in virulence. In the present study, a mass spectrometry-based, label-free relative quantitative proteomics approach was used to investigate the proteins expressed by the wild strain, B. melitensis biovar 3 and compare it with those expressed by B. melitensis M5-90. The higher level of virulence for B. melitensis biovar 3 compared to B. melitensis M5-90 was validated in vitro and in vivo. A total of 2133 proteins, encompassing 68% of the theoretical proteome, were identified and quantified by proteomic analysis, resulting in broad coverage of the B. melitensis proteome. A total of 147 proteins were identified as differentially expressed (DE) between these two strains. In addition, 9 proteins and 30 proteins were identified as unique to B. melitensis M5-90 and B. melitensis biovar 3, respectively. Pathway analysis revealed that the majority of the DE proteins were involved in iron uptake, quorum sensing, pyrimidine metabolism, glycine betaine biosynthetic and metabolic processes, thiamine-containing compound metabolism and ABC transporters. The expression of BtpA and VjbR proteins (two well-known virulence factors) in B. melitensis biovar 3 was 8-fold and 2-fold higher than in B. melitensis M5-90. In summary, our results identified many unique proteins that could be selected as candidate markers for differentiating vaccinated animals from animals with wild-type infections. BtpA and VjbR proteins might be responsible for the residual virulence of B. melitensis M5-90, while ABC transporters and thiamine metabolism associated proteins may be newly identified Brucella virulence factors. All of the identified DE proteins provide valuable information for the development of vaccines and the discovery of novel therapeutic targets

The time-depth of Corded Ware burial landscapes: A comparative study of Single Grave and Battle Axe burial alignments in Denmark, The Netherlands and Sweden

Barrow landscapes appeared in the third and second millennia BC throughout North-Western Europe; these first barrows were constructed by people of the Corded Ware culture and placed in alignments. This thesis is an interregional comparative study, to determine whether there is a pattern in the time-depths of the burial alignments of Trehuse-Sjørup-Dollerup in Denmark, Angelso-Emmerhout in The Netherlands and Lilla Beddinge in Sweden. The analysis is conducted by means of a literature study and the application of typochronologies. In recent research, the Corded Ware ‘culture’ is still seen as a widespread, unified social phenomenon that is the result of migration, but more emphasis is placed on the regional variability of this phenomenon. Regional variability is also what we see in the three case-studies; in fact, perhaps one may better speak of ‘local variability’, as each case-study reveals a remarkable variety even within one alignment. Even though there do seem to be interregionally shared traits, these are expressed in local practices. Despite the limitations of establishing a time-depth by means of typochronologies, all three alignments reveal a long use-life; even in the Bronze and Iron Ages, prehistoric people buried their dead here. Temporality seems to have been an important aspect of the ‘Corded Ware’ burial landscape

Kenya: West Kenya postmarks

HiWATER: The Multi-Scale Observation Experiment on Evapotranspiration over heterogeneous land surfaces (MUSOEXE) Dataset - Flux Observation Matrix (stable isotopic observations

Collaborative mental health care : changing the landscape of mental health care?

In this thesis two major changes in the organization of mental health care delivery are explored. The first is collaborative mental health care in primary care, developed as an alternative way to treat common mental health disorders compared to the traditional referral and treatment practice. The collaborative care program followed the principles of stepped care. The first and least intensive treatment step was provided within the collaborative care program in the primary care setting. Treatment intensity was only stepped up through referral to specialized mental health care for patients who did not sufficiently respond to the first step. The traditional practice was direct referral and treatment within specialized care. In several studies we investigated effectiveness, short- and long-term efficiency, cost-effectiveness and whether the stepped care approach was appropriate for all patients instead of the matched care approach. The second change was the integration of eHealth in the collaborative care treatment model. In this study, implementation factors that could either inhibit or promote the uptake and utilization of blended collaborative care by mental health professionals and patients were assessed