Adaptive plasticity during stress and depression and the role of glutamate-nitric oxide pathways

Anxiety and mood disorders are amongst the most prevalent and disabling of all the psychiatric disorders. Under-diagnosis and current treatments that are often less than adequately effective, contributes to an enormous personal and economic cost to the patient, family and health-care organizations. Although distinctly separate disorders at neuropathological and phenomenological levels, brain-imaging studies in posttraumatic stress disorder (PTSD) and depression have emphasized that both illnesses may induce damaging effects on regions of the brain involved in regulating the response to stress. While controversy prevails as to whether these changes represent an adaptive process or are indeed pathological, they are associated with marked changes in memory and other cognitive functions. In depression, a history of prior episodes is correlated with a higher risk of relapse, while poor compliance with antidepressants not only predicts later relapse, it may result in a more rapid shrinkage of the abovementioned brain regions, possibly providing a basis for relapse and treatment resistance. Similarly, even with the introduction of effective medications for PTSD, many patients remain treatment-resistant. Stress in various guises may alter synaptic connectivity in the brain by bolstering glutamatergic excitotoxic mechanisms. Understanding these mechanisms may assist in developing more effective treatment strategies. This paper will review pre-clinical and clinical evidence supporting a role for the glutamatenitric oxide pathway as a putative mediator of the neuropathological changes evident in depression and stress-related disorders, particularly PTSD, and its potential as a novel target for psychotropic activity. South African Psychiatry Review Vol. 9(3) 2006: 132-13

Learning to segment when experts disagree

Recent years have seen an increasing use of supervised learning methods for segmentation tasks. However, the predictive performance of these algorithms depend on the quality of labels, especially in medical image domain, where both the annotation cost and inter-observer variability are high. In a typical annotation collection process, different clinical experts provide their estimates of the “true” segmentation labels under the influence of their levels of expertise and biases. Treating these noisy labels blindly as the ground truth can adversely affect the performance of supervised segmentation models. In this work, we present a neural network architecture for jointly learning, from noisy observations alone, both the reliability of individual annotators and the true segmentation label distributions. The separation of the annotators’ characteristics and true segmentation label is achieved by encouraging the estimated annotators to be maximally unreliable while achieving high fidelity with the training data. Our method can also be viewed as a translation of STAPLE, an established label aggregation framework proposed in Warfield et al. [1] to the supervised learning paradigm. We demonstrate first on a generic segmentation task using MNIST data and then adapt for usage with MRI scans of multiple sclerosis (MS) patients for lesion labelling. Our method shows considerable improvement over the relevant baselines on both datasets in terms of segmentation accuracy and estimation of annotator reliability, particularly when only a single label is available per image. An open-source implementation of our approach can be found at https://github.com/UCLBrain/MSLS

Practicing physiotherapy in Danish private practice: an ethical perspective.

Despite an increasingly growth of professional guidelines, textbooks and research about ethics in health care, awareness about ethics in Danish physiotherapy private practice seen vague. This article explores how physiotherapists in Danish private practice, from an ethical perspective, perceive to practice physiotherapy. The empirical data consists of interviews with twenty-one physiotherapists. The interviews are analysed from a hermeneutic approach, inspired by Ricoeur's textual interpretation of distanciation. The analysis follows three phases: naïve reading, structural analysis and comprehensive analysis. Four main themes are constructed: Beneficence as the driving force; Disciplining the patient through the course of physiotherapy; Balancing between being a trustworthy professional and a businessperson; The dream of a code of practice. Private practice physiotherapy is embedded in a structural frame directed by both political and economical conditions that shape the conditions for practicing physiotherapy. It means that beneficence in practice is a balance between the patient, the physiotherapists themselves and the business. Beneficence towards the patient is expressed as an implicit demand. Physiotherapeutic practice is expressed as being an integration of professionalism and personality which implies that the physiotherapists also have to benefit themselves. Private practice seems to be driven by a paternalistic approach towards the patient, where disciplining the patient is a crucial element of practice, in order to optimise profit. Physiotherapists wish for a more beneficent practice in the future by aiming at bridging 'to be' and 'ought to be'

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

The more the merrier? Increasing group size may be detrimental to decision-making performance in nominal groups

<div><p>Demonstrability—the extent to which group members can recognize a correct solution to a problem—has a significant effect on group performance. However, the interplay between group size, demonstrability and performance is not well understood. This paper addresses these gaps by studying the joint effect of two factors—the difficulty of solving a problem and the difficulty of verifying the correctness of a solution—on the ability of groups of varying sizes to converge to correct solutions. Our empirical investigations use problem instances from different computational complexity classes, NP-Complete (NPC) and PSPACE-complete (PSC), that exhibit similar solution difficulty but differ in verification difficulty. Our study focuses on nominal groups to isolate the effect of problem complexity on performance. We show that NPC problems have higher demonstrability than PSC problems: participants were significantly more likely to recognize correct and incorrect solutions for NPC problems than for PSC problems. We further show that increasing the group size can actually <i>decrease</i> group performance for some problems of low demonstrability. We analytically derive the boundary that distinguishes these problems from others for which group performance monotonically improves with group size. These findings increase our understanding of the mechanisms that underlie group problem-solving processes, and can inform the design of systems and processes that would better facilitate collective decision-making.</p></div

Host Suitability of a Gregarious Parasitoid on Beetle Hosts: Flexibility between Fitness of Adult and Offspring

Behavioral tactics play a crucial role in the evolution of species and are likely to be found in host-parasitoid interactions where host quality may differ between host developmental stages. We investigated foraging decisions, parasitism and related fitness in a gregarious ectoparasitoid, Sclerodermus harmandi in relation to two distinct host developmental stages: larvae and pupae. Two colonies of parasitoids were reared on larvae of Monochamus alternatus and Saperda populnea (Cerambycidae: Lamiinae). Paired-choice and non-choice experiments were used to evaluate the preference and performance of S. harmandi on larvae and pupae of the two species. Foraging decisions and offspring fitness-related consequences of S. harmandi led to the selection of the most profitable host stage for parasitoid development. Adult females from the two colonies oviposited more quickly on pupae as compared to larvae of M. alternatus. Subsequently, their offspring development time was faster and they gained higher body weight on the pupal hosts. This study demonstrates optimal foraging of intraspecific détente that can occur during host-parasitoid interactions, of which the quality of the parasitism (highest fitness benefit and profitability) is related to the host developmental stage utilized. We conclude that S. harmandi is able to perfectly discriminate among host species or stages in a manner that maximizes its offspring fitness. The results indicated that foraging potential of adults may not be driven by its maternal effects, also induced flexibly with encountering prior host quality

Effects of N-Glycosylation Site Removal in Archaellins on the Assembly and Function of Archaella in Methanococcus maripaludis

In Methanococcus maripaludis S2, the swimming organelle, the archaellum, is composed of three archaellins, FlaB1S2, FlaB2S2 and FlaB3S2. All three are modified with an N-linked tetrasaccharide at multiple sites. Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). Of the 6 double-site mutation complementations all were archaellated except D1,3. Of the 4 triple-site mutation complements, only D2,3,4 was archaellated. Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. All complementations that led to a return of archaella also resulted in motile cells with the exception of the D4 version. In addition, a series of FlaB2S2 scanning deletions each missing 10 amino acids was also generated and tested for their ability to complement the ΔflaB2S2 strain. While most variants were expressed, none of them restored archaellation, although FlaB2S2 harbouring a smaller 3-amino acid deletion was able to partially restore archaellation

Treatment delay of bone tumours, compilation of a sociodemographic risk profile: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Bone tumours are comparatively rare tumours and delays in diagnosis and treatment are common. The purpose of this study was to analyse sociodemographic risk factors for bone tumour patients in order to identify those at risk of prolonged patients delay (time span from first symptoms to consultation), professional delay (from consultation to treatment) or symptom interval (from first symptoms to treatment). Understanding these relationships might enable us to shorten time to diagnosis and therapy.</p> <p>Methods</p> <p>We carried out a retrospective analysis of 265 patients with bone tumours documenting sociodemographic factors, patient delay, professional delay and symptom interval. A multivariate explorative Cox model was performed for each delay.</p> <p>Results</p> <p>Female gender was associated with a prolonged patient delay. Age under 30 years and rural living predisposes to a prolonged professional delay and symptom interval.</p> <p>Conclusion</p> <p>Early diagnosis and prompt treatment are required for successful management of most bone tumour patients. We succeeded in identifying the histology independent risk factors of age under 30 years and rural habitation for treatment delay in bone tumour patients. Knowing about the existence of these risk groups age under 30 years and female gender could help the physician to diagnose bone tumours earlier. The causes for the treatment delays of patients living in a rural area have to be investigated further. If the delay initiates in the lower education of rural general physicians, further training about bone tumours might advance early detection. Hence the outcome of patients with bone tumours could be improved.</p