Dependence in Man Parens, Henri; Saul, Leon J.
1971, 2014, 2014-04-14, 2019-07-09
eBook
In this classic study, Henri Parens and Leon J. Saul provide a comprehensive review of Freud's writings on the subject of dependence, drawing attention to the fact that Freud said much more about ...dependence than is generally recognised. The authors proceed to supplement the theory of dependence from their own perspective, drawing on the formulations of Rene Spitz and the findings of ethologists (especially in imprinting and primary socialization) in order to shed further light on the singularity of early human development. They postulate the libidinization of dependence and trace the effects of this on psychic development, and also consider the dependence continuum in dynamic and economic terms ("inner sustainment"), which reflects the equilibrium between dependency and self-reliance. Utilising Anna Freud's developmental lines and Margaret Mahler's subphases of separation and individuation, they trace the epigenesis of dependence and provide illuminating clinical examples.In both its theoretical formulations and its clinical implications, this book will be of interest to psychoanalysts, psychiatrists, and to clinicians in allied fields. The recognition of normative dependence brings pathological dependence into clearer focus, thus refining assessments of dependence in treatment and offering a more discriminating frame of reference for teaching and research. Because it focuses on normative aspects of dependence, this book will provide a fresh orientation for all students of human behavior and will undoubtedly raise many questions and stimulate further research.
Cardiomyocytes and endothelial cells in the heart are in close proximity and in constant dialogue. Endothelium regulates the size of the heart, supplies oxygen to the myocardium and secretes factors ...that support cardiomyocyte function. Robust and predictive cardiac disease models that faithfully recapitulate native human physiology
would therefore ideally incorporate this cardiomyocyte-endothelium crosstalk. Here, we have generated and characterized human cardiac microtissues
that integrate both cell types in complex 3D structures. We established conditions for simultaneous differentiation of cardiomyocytes and endothelial cells from human pluripotent stem cells following initial cardiac mesoderm induction. The endothelial cells expressed cardiac markers that were also present in primary cardiac microvasculature, suggesting cardiac endothelium identity. These cell populations were further enriched based on surface markers expression, then recombined allowing development of beating 3D structures termed cardiac microtissues. This
model was robustly reproducible in both embryonic and induced pluripotent stem cells. It thus represents an advanced human stem cell-based platform for cardiovascular disease modelling and testing of relevant drugs.
Antibiotics have played a critical role in the prevention, control, and treatment of bacterial diseases in humans and animals, and as growth promoters (AGPs) when used at sub-therapeutic ...concentrations in animal production. Numerous hypotheses have been proposed for the effectiveness of AGPs, which have largely centered on the beneficial modulation of the intestinal microbiota. However, these hypotheses have been doubted by some researchers, as AGPs are fed at concentrations that would typically be below minimum inhibitory concentrations (sub-MIC) for the antibiotic used. More recently, pro-inflammatory immune responses have been associated with poor growth performance, and this, along with reported direct, anti-inflammatory effects of some antibiotics, have led to suggestions that reducing the nutrient cost of (intestinal) inflammation may explain the growth promoting or permitting effect of AGPs. However, doubts about antibacterial effects of AGPs, and the search for alternative explanations, overlook the sub-MIC effects of antibiotics. This paper summarizes some of the reported sub-MIC effects of antibiotics and considers these in the context of helping to explain the mode of action of AGPs and effects seen in studies in vivo. This leads to suggestions for the features that alternatives to AGPs could exhibit to achieve similar performance efficacy as AGPs.
Abstract
The gut barrier, comprising the microbiota and their products, mucus layers, host-derived antimicrobial compounds e.g., host defense peptides (HDP), IgA, epithelium, and underlying immune ...tissues, performs the essential function of preventing the passage of harmful microorganisms and substances into the body, while enabling the acquisition of dietary nutrients. Antibiotic growth promoters (AGP) are widely accepted as the "gold standard" of performance-enhancing feed additives, which had become integral and valuable components of modern, efficient animal production, but are now being phased out in many parts of the world. This review, therefore, examines the reported effects of AGP on the key components of gut barrier function, particularly where corresponding (positive) growth performance data were provided to indicate that any changes were beneficial, and some important trends do emerge. Certain bacterial families (e.g., Lachnospiraceae), genera (e.g., Faecalibacterium, Propionibacterium, and Ruminococcus), or species (e.g., F. prausnitzii, B. fragilis, and some Lactobacillus spp.) have been reported to increase with AGP use, are associated with improved growth performance, and show benefit across species, which may be related to their production of short-chain fatty acids (SCFA). Various studies have investigated the effects of AGP on mucus-related parameters (e.g., goblet cell size, density, and mucin mRNA expression) but these do not always seem to correlate well with the actual physical characteristics of the mucus layer(s). Surprisingly, there are little data relating to HDP or IgA, even though they have recognized benefits. There are clear AGP benefits on epithelial structure and function (e.g., nutrient digestibility), and these may (currently) provide the most reliable indicators of the efficacy of growth promoters. Data investigating effects on gut immune parameters (e.g., cell populations, cytokines, and chemokines), with corresponding growth performance, are limited and require further detailed interrogation. This review highlights both important observations related to the effects of AGP on key gut barrier components, with associated growth performance, and areas that require further investigation, thus providing an informative basis for assessing the potential of AGP alternatives.
Peat forming Sphagnum mosses are able to prevent the dominance of vascular plants under ombrotrophic conditions by efficiently scavenging atmospherically deposited nitrogen (N). N-uptake kinetics of ...these mosses are therefore expected to play a key role in differential N availability, plant competition, and carbon sequestration in Sphagnum peatlands. The interacting effects of rain N concentration and exposure time on moss N-uptake rates are, however, poorly understood. We investigated the effects of N-concentration (1, 5, 10, 50, 100, 500 µM), N-form ((15)N-ammonium or nitrate) and exposure time (0.5, 2, 72 h) on uptake kinetics for Sphagnum magellanicum from a pristine bog in Patagonia (Argentina) and from a Dutch bog exposed to decades of N-pollution. Uptake rates for ammonium were higher than for nitrate, and N-binding at adsorption sites was negligible. During the first 0.5 h, N-uptake followed saturation kinetics revealing a high affinity (Km 3.5-6.5 µM). Ammonium was taken up 8 times faster than nitrate, whereas over 72 hours this was only 2 times. Uptake rates decreased drastically with increasing exposure times, which implies that many short-term N-uptake experiments in literature may well have overestimated long-term uptake rates and ecosystem retention. Sphagnum from the polluted site (i.e. long-term N exposure) showed lower uptake rates than mosses from the pristine site, indicating an adaptive response. Sphagnum therefore appears to be highly efficient in using short N pulses (e.g. rainfall in pristine areas). This strategy has important ecological and evolutionary implications: at high N input rates, the risk of N-toxicity seems to be reduced by lower uptake rates of Sphagnum, at the expense of its long-term filter capacity and related competitive advantage over vascular plants. As shown by our conceptual model, interacting effects of N-deposition and climate change (changes in rainfall) will seriously alter the functioning of Sphagnum peatlands.
•The gut microbiome comprises a large mass of microbes and their associated genes.•The gut microbiome profoundly influences immune system development.•Host and environmental factors affect microbiome ...establishment and stability.•Microbiome modification provides challenges and opportunities for bird health.•Future research will better inform modification of microbiome-host interactions.
Most animals are colonised by at least as many microbial cells as somatic cells, potentially comprising at least 100 times more genes within just the gut microbiota than the host itself. It is, therefore, evident that such a conglomeration can have a profound effect on various bodily systems, particularly the (gut) immune system. Chickens are major providers of efficiently produced protein for humans but also harbour common foodborne pathogens and are susceptible to significant and costly diseases, making a thorough understanding of the influence of the gut microbiome on the immune system very pertinent. Major colonisation of the chicken intestine occurs after hatch and this, along with subsequent microbiota composition and activity, are influenced by numerous host and environmental factors, such that each individual has a unique microbiome signature. However, both extreme (e.g. germ free) and more subtle (e.g. diet changes) microbiome modifications can profoundly impact the development of the gut immune system, particularly adaptive immune apparatus and function. This review will consider the influence of the chicken gut microbiome on immune system development, the implications of this relationship in terms of disease susceptibility, vaccine response, optimal health and productivity, and thus exogenous approaches to positively shape microbiome-immune system interactions.
Tandem devices combining perovskite and silicon solar cells are promising candidates to achieve power conversion efficiencies above 30% at reasonable costs. State-of-the-art monolithic two-terminal ...perovskite/silicon tandem devices have so far featured silicon bottom cells that are polished on their front side to be compatible with the perovskite fabrication process. This concession leads to higher potential production costs, higher reflection losses and non-ideal light trapping. To tackle this issue, we developed a top cell deposition process that achieves the conformal growth of multiple compounds with controlled optoelectronic properties directly on the micrometre-sized pyramids of textured monocrystalline silicon. Tandem devices featuring a silicon heterojunction cell and a nanocrystalline silicon recombination junction demonstrate a certified steady-state efficiency of 25.2%. Our optical design yields a current density of 19.5 mA cm
thanks to the silicon pyramidal texture and suggests a path for the realization of 30% monolithic perovskite/silicon tandem devices.
The last decade of research into the pharmacogenetics of antipsychotics has seen the development of genetic tests to determine the patients' metabolic status and the first attempts at personalization ...of antipsychotic treatment. The most significant results are the association between drug metabolic polymorphisms, mainly in cytochrome P450 genes, with variations in drug metabolic rates and side effects. Patients with genetically determined CYP2D6 poor metabolizer (PMs) status may require lower doses of antipsychotic. Alternatively, CYP2D6 ultrarapid matabolizers (UMs) will need increased drug dosage to obtain therapeutic response. Additionally, polymorphisms in dopamine and serotonin receptor genes are repeatedly found associated with response phenotypes, probably reflecting the strong affinities that most antipsychotics display for these receptors. In particular, there is important evidence suggesting association between dopamine 2 receptor (D2) polymorphisms (Taq I and -141-C Ins/Del) and a dopamine 3 receptor (D3) polymorphism (Ser9Gly) with antipsychotic response and drug-induced tardive dyskinesia. Additionally, there is accumulating evidence indicating the influence of a 5-HT2C polymorphism (-759-T/C) in antipsychotic-induced weight gain. Application of this knowledge to clinical practice is slowly gathering pace, with pretreatment determination of individual's drug metabolic rates, via CYP genotyping, leading the field. Genetic determination of patients' metabolic status is expected to bring clinical benefits by helping to adjust therapeutic doses and reduce adverse reactions. Genetic tests for the pretreatment prediction of antipsychotic response, although still in its infancy, have obvious implications for the selection and improvement of antipsychotic treatment. These developments can be considered as successes, but the objectives of bringing pharmacogenetic and pharmacogenomic research in psychiatric clinical practice are far from being realized. Further development of genetic tests is required before the concept of tailored treatment can be applied to psychopharmatherapy. This review aims to summarize the key findings from the last decade of research in the field. Current knowledge on genetic prediction of drug metabolic status, general response and drug-induced side effects will be reviewed and future pharmacogenomic and epigenetic research will be discussed.
Abstract Several potential disease-modifying drugs for Alzheimer's disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are ...already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42 ) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF biomarkers for both clinical trials and routine clinical diagnosis of AD.
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