What is psychiatry? Co-producing complexity in mental health

What is psychiatry? Such a question is increasingly important to engage with in light of the development of new diagnostic frameworks that have wide-ranging and international clinical and societal implications. I suggest in this reflective essay that ‘psychiatry' is not a singular entity that enjoins consistent forms of critique along familiar axes; rather, it is a heterogeneous assemblage of interacting material and symbolic elements (some of which endure, and some of which are subject to innovation). In underscoring the diversity of psychiatry, I seek to move towards further sociological purchase on what remains a contested and influential set of discourses and practices. This approach foregrounds the relationships between scientific knowledge, biomedical institutions, social action and subjective experience; these articulations co-produce both psychiatry and each other. One corollary of this emphasis on multiplicity and incoherence within psychiatric theory, research and practice, is that critiques which elide this complexity are rendered problematic. Engagements with psychiatry are, I argue, best furthered by recognising its multifaceted nature

Проблемы увеличения продуктивности АПК в Украине и пути повышения его потенциала

Целью статьи является изучение причин снижения показателей продуктивности в агропромышленном комплексе и путей повышения продуктивности сельскохозяйственных культур

Toxoplasma Effector MAF1 Mediates Recruitment of Host Mitochondria and Impacts the Host Response

Recent information has revealed the functional diversity and importance of mitochondria in many cellular processes including orchestrating the innate immune response. Intriguingly, several infectious agents, such as Toxoplasma, Legionella, and Chlamydia, have been reported to grow within vacuoles surrounded by host mitochondria. Although many hypotheses have been proposed for the existence of host mitochondrial association (HMA), the causes and biological consequences of HMA have remained unanswered. Here we show that HMA is present in type I and III strains of Toxoplasma but missing in type II strains, both in vitro and in vivo. Analysis of F1 progeny from a type II×III cross revealed that HMA is a Mendelian trait that we could map. We use bioinformatics to select potential candidates and experimentally identify the polymorphic parasite protein involved, mitochondrial association factor 1 (MAF1). We show that introducing the type I (HMA+) MAF1 allele into type II (HMA-) parasites results in conversion to HMA+ and deletion of MAF1 in type I parasites results in a loss of HMA. We observe that the loss and gain of HMA are associated with alterations in the transcription of host cell immune genes and the in vivo cytokine response during murine infection. Lastly, we use exogenous expression of MAF1 to show that it binds host mitochondria and thus MAF1 is the parasite protein directly responsible for HMA. Our findings suggest that association with host mitochondria may represent a novel means by which Toxoplasma tachyzoites manipulate the host. The existence of naturally occurring HMA+ and HMA- strains of Toxoplasma, Legionella, and Chlamydia indicates the existence of evolutionary niches where HMA is either advantageous or disadvantageous, likely reflecting tradeoffs in metabolism, immune regulation, and other functions of mitochondria. © 2014 Pernas et al

Overall Survival Time Prediction for High-grade Glioma Patients based on Large-scale Brain Functional Networks

High-grade glioma (HGG) is a lethal cancer with poor outcome. Accurate preoperative overall survival (OS) time prediction for HGG patients is crucial for treatment planning. Traditional presurgical and noninvasive OS prediction studies have used radiomics features at the local lesion area based on the magnetic resonance images (MRI). However, the highly complex lesion MRI appearance may have large individual variability, which could impede accurate individualized OS prediction. In this paper, we propose a novel concept, namely brain connectomics-based OS prediction. It is based on presurgical resting-state functional MRI (rs-fMRI) and the non-local, large-scale brain functional networks where the global and systemic prognostic features rather than the local lesion appearance are used to predict OS. We propose that the connectomics features could capture tumor-induced network-level alterations that are associated with prognosis. We construct both low-order (by means of sparse representation with regional rs-fMRI signals) and high-order functional connectivity (FC) networks (characterizing more complex multi-regional relationship by synchronized dynamics FC time courses). Then, we conduct a graph-theoretic analysis on both networks for a jointly, machine-learning-based individualized OS prediction. Based on a preliminary dataset (N = 34 with bad OS, mean OS, ~400 days; N = 34 with good OS, mean OS, ~1030 days), we achieve a promising OS prediction accuracy (86.8%) on separating the individuals with bad OS from those with good OS. However, if using only conventionally derived descriptive features (e.g., age and tumor characteristics), the accuracy is low (63.2%). Our study highlights the importance of the rs-fMRI and brain functional connectomics for treatment planning

Broadened T-cell Repertoire Diversity in ivIg-treated SLE Patients is Also Related to the Individual Status of Regulatory T-cells

Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density.Octapharma research funding; Fundação para a Ciência e a Tecnologia postdoctoral fellowships: (SFRH/BPD/20806/2004, SFRH/BPD/34648/2007); FCT Programa Pessoa travel grant

Infection of Cultured Human Endothelial Cells by Legionella pneumophila

Legionella pneumophila is a gram-negative pathogen that causes a severe pneumonia known as Legionnaires' disease. Here, we demonstrate for the first time that L. pneumophila infects and grows within cultured human endothelial cells. Endothelial infection may contribute to lung damage observed during Legionnaires' disease and to systemic spread of this organism

Toll-Like Receptor 3 Signaling on Macrophages Is Required for Survival Following Coxsackievirus B4 Infection

Toll-like receptor 3 (TLR3) has been proposed to play a central role in the early recognition of viruses by sensing double stranded RNA, a common intermediate of viral replication. However, several reports have demonstrated that TLR3 signaling is either dispensable or even harmful following infection with certain viruses. Here, we asked whether TLR3 plays a role in the response to coxsackievirus B4 (CB4), a prevalent human pathogen that has been associated with pancreatitis, myocarditis and diabetes. We demonstrate that TLR3 signaling on macrophages is critical to establish protective immunity to CB4. TLR3 deficient mice produced reduced pro-inflammatory mediators and are unable to control viral replication at the early stages of infection resulting in severe cardiac damage. Intriguingly, the absence of TLR3 did not affect the activation of several key innate and adaptive cellular effectors. This suggests that in the absence of TLR3 signaling on macrophages, viral replication outpaces the developing adaptive immune response. We further demonstrate that the MyD88-dependent signaling pathways are not only unable to compensate for the loss of TLR3, they are also dispensable in the response to this RNA virus. Our results demonstrate that TLR3 is not simply part of a redundant system of viral recognition, but rather TLR3 plays an essential role in recognizing the molecular signatures associated with specific viruses including CB4

Neural Substrates for the Motivational Regulation of Motor Recovery after Spinal-Cord Injury

It is believed that depression impedes and motivation enhances functional recovery after neuronal damage such as spinal-cord injury and stroke. However, the neuronal substrate underlying such psychological effects on functional recovery remains unclear. A longitudinal study of brain activation in the non-human primate model of partial spinal-cord injury using positron emission tomography (PET) revealed a contribution of the primary motor cortex (M1) to the recovery of finger dexterity through the rehabilitative training. Here, we show that activity of the ventral striatum, including the nucleus accumbens (NAc), which plays a critical role in processing of motivation, increased and its functional connectivity with M1 emerged and was progressively strengthened during the recovery. In addition, functional connectivities among M1, the ventral striatum and other structures belonging to neural circuits for processing motivation, such as the orbitofrontal cortex, anterior cingulate cortex and pedunculopontine tegmental nucleus were also strengthened during the recovery. These results give clues to the neuronal substrate for motivational regulation of motor learning required for functional recovery after spinal-cord injury