Electroconvulsive Treatment: Hypotheses about Mechanisms of Action

No consensus has been reached on the mode of action of electroconvulsive treatment (ECT). We suggest that two features may aid in the delineation of the involved mechanisms. First, when effective, ECT would be likely to affect brain functions that are typically altered in its primary recipient group, people with severe depression. Central among these are the frontal and temporal lobes, the hypothalamus-pituitary-adrenal (HPA) stress axis, and the mesocorticolimbic dopamine system. Second, the involved mechanisms should be affected for a time period that matches the average endurance of clinical effects, which is indicated to be several days to a few weeks. To identify effects upon frontal and temporal lobe functioning we reviewed human studies using EEG, PET, SPECT, and fMRI. Effects upon the HPA axis and the dopamine system were assessed by reviewing both human and animal studies. The EEG studies indicate that ECT decelerates neural activity in the frontal and temporal lobes (increased delta and theta wave activity) for weeks to months. Comparable findings are reported from PET and SPECT studies, with reduced cerebral blood flow (functional deactivation) for weeks to months after treatment. The EEG deceleration and functional deactivation following ECT are statistically associated with reduced depression scores. FMRI studies indicate that ECT flattens the pattern of activation and deactivation that is associated with cognitive task performance and alters cortical functional connectivity in the ultra slow frequency range. A common finding from human and animal studies is that ECT acutely activates both the HPA axis and the dopamine system. In considering this evidence, we hypothesize that ECT affects the brain in a similar manner as severe stress or brain trauma which activates the HPA axis and the dopamine system and may compromise frontotemporal functions

Molecular Carbon Chains and Rings in TMC-1

We present mapping results in several rotational transitions of HC3N, C6H, both cyclic and linear C3H2 and C3H, towards the cyanopolyyne peak of the filamentary dense cloud TMC-1 using the IRAM 30m and MPIfR 100m telescopes. The spatial distribution of the cumulene carbon chain propadienylidene H2C3 (hereafter l-C3H2) is found to deviate significantly from the distributions of the cyclic isomer c-C3H2, HC3N, and C6H which in turn look very similar. The cyclic over linear abundance ratio of C3H2 increases by a factor of 3 across the filament, with a value of 28 at the cyanopolyyne peak. This abundance ratio is an order of magnitude larger than the range (3 to 5) we observed in the diffuse interstellar medium. The cyclic over linear abundance ratio of C3H also varies by ~2.5 in TMC-1, reaching a maximum value (13) close to the cyanopolyyne peak. These behaviors might be related to competitive processes between ion-neutral and neutral-neutral reactions for cyclic and linear species.Comment: Accepted for publication in The Astrophysical Journal, part I. 24 pages, including 4 tables, 7 figures, and figure caption

Evolution of an elliptical bubble in an accelerating extensional flow

Mathematical models that describe the dynamical behavior of a thin gas bubble embedded in a glass fiber during a fiber drawing process have been discussed and analyzed. The starting point for the mathematical modeling was the equations presented in [1] for a glass fiber with a hole undergoing extensional flow. These equations were reconsidered here with the additional reduction that the hole, i.e. the gas bubble, was thin as compared to the radius of the fiber and of finite extent. The primary model considered was one in which the mass of the gas inside the bubble was fixed. This fixed-mass model involved equations for the axial velocity and fiber radius, and equations for the radius of the bubble and the gas pressure inside the bubble. The model equations assumed that the temperature of the furnace of the drawing tower was known. The governing equations of the bubble are hyperbolic and predict that the bubble cannot extend beyond the limiting characteristics specified by the ends of the initial bubble shape. An analysis of pinch-off was performed, and it was found that pinch-off can occur, depending on the parameters of the model, due to surface tension when the bubble radius is small. In order to determine the evolution of a bubble, a numerical method of solution was presented. The method was used to study the evolution of two different initial bubble shapes, one convex and the other non-convex. Both initial bubble shapes had fore-aft symmetry, and it was found that the bubbles stretched and elongated severely during the drawing process. For the convex shape, fore-aft symmetry was lost in the middle of the drawing process, but the symmetry was re-gained by the end of the drawing tower. A small amount of pinch-off was observed at each end for this case, so that the final bubble length was slightly shorter than its theoretical maximum length. For the non-convex initial shape, pinch-off occurred in the middle of the bubble resulting in two bubbles by the end of the fiber draw. The two bubbles had different final pressures and did not have fore-aft symmetry. An extension of the fixed-mass model was considered in which the gas in the bubble was allowed to diffuse into the surrounding glass. The governing equations for this leaky-mass model were developed and manipulated into a form suitable for a numerical treatment

Native valve endocarditis due to Micrococcus luteus: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p><it>Micrococcus luteus </it>endocarditis is a rare case of infective endocarditis. A total of 17 cases of infective endocarditis due to <it>M luteus </it>have been reported in the literature to date, all involving prosthetic valves. To the best of our knowledge, we describe the first case of native aortic valve <it>M luteus </it>endocarditis in an immunosuppressed patient in this report.</p> <p>Case report</p> <p>A 74-year-old Greek-Cypriot woman was admitted to our Internal Medicine Clinic due to fever and malaise and the diagnosis of aortic valve <it>M luteus </it>endocarditis was made. She was immunosuppressed due to methotrexate and steroid treatment. Our patient was unsuccessfully treated with vancomycin, gentamicin and rifampicin for four weeks. The aortic valve was replaced and she was discharged in good condition.</p> <p>Conclusions</p> <p>Prosthetic infective endocarditis due to <it>M luteus </it>is rare. To the best of our knowledge, we report the first case in the literature involving a native valve.</p

Biodistribution et toxicité des nanocapsules chargées en 188Re après injection intratumorale par convection enhanced delivery chez la souris

Objectifs Déterminer la faisabilité, l’intérêt et la toxicité hématologique de l’administration intratumorale par convection enhanced delivery (CED) de nanocapsules chargées en 188Re (NCL-188Re). Matériels et méthodes L’étude de biodistribution des NCL-188Re vs perrhénate (188ReO4−) a été réalisée sur des souris nude (n = 30). Les animaux ont été séparés en 2 groupes : injection intratumorale de 188ReO4− pour le premier groupe (n = 15, 3 MBq) et de NCL-188Re pour le second groupe (n = 15, 3 MBq). Les animaux ont été sacrifiés à 1 h (n = 10), 24 h (n = 10) et 72 h (n = 10) après l’injection, les organes prélevés et comptés. La toxicité hématologique des NCL-188Re a été évaluée par prises de sang de 50 μL (sinus rétro-orbitaire) réalisées à j2, j7, j14 et j21 après traitement par NaCl (n = 4), NCL-188Re (3 MBq, n = 4), NCL-188Re (6 MBq, n = 4) et NCL-188Re (12 MBq, n = 4). Résultats La vectorisation par NCL a permis de limiter l’élimination urinaire du 188Re puisque dès 24 h post-IV 0,1 ± 0,1 % de la dose injectée (%D.I.) vs 81,9 ± 7,5 % D.I. sont retrouvés dans les urines pour les formes NCL188Re-SSS et 188ReO4-, respectivement, (p = 0,016). Celle-ci permet également de retrouver une activité significativement supérieure dans la tumeur à tous les temps de l’étude. L’administration unique de NCL-188Re a induit une toxicité modérée pour les activités injectées les plus élevées (12 MBq) se manifestant principalement par une thrombopénie transitoire de nadir j14–j18. Il n’a pas été observé de toxicité au niveau des autres lignées cellulaires pour les activités administrées de 3 et 6 MBq. Conclusions Les résultats obtenus montrent la faisabilité de l’injection intratumorale par CED et l’intérêt de la vectorisation du 188Re par les NCL. Les premiers signes de toxicité hématologiques sont en faveur du fractionnement des doses administrées et d’un meilleur ciblage par fonctionnalisation des NCL aux oestrogènes pour permettre une meilleure rétention tumorale

Factors affecting mechanical (nociceptive) thresholds in piglets

AbstractObjectiveTo evaluate the stability and repeatability of measures of mechanical (nociceptive) thresholds in piglets and to examine potentially confounding factors when using a hand held algometer.Study designDescriptive, prospective cohort.AnimalsForty-four piglets from four litters, weighing 4.6 ± 1.0 kg (mean ± SD) at 2 weeks of age.MethodsMechanical thresholds were measured twice on each of 2 days during the first and second week of life. Data were analyzed using a repeated measures design to test the effects of behavior prior to testing, sex, week, day within week, and repetition within day. The effect of body weight and the interaction between piglet weight and behaviour were also tested. Piglet was entered into the model as a random effect as an additional test of repeatability. The effect of repeated testing was used to test the stability of measures. Pearson correlations between repeated measures were used to test the repeatability of measures. Variance component analysis was used to describe the variability in the data.ResultsVariance component analysis indicated that piglet explained only 17% of the variance in the data. All variables in the model (behaviour prior to testing, sex, week, day within week, repetition within day, body weight, the interaction between body weight and behaviour, piglet identity) except sex had a significant effect (p < 0.04 for all). Correlations between repeated measures increased from the first to the second week.Conclusions and Clinical relevanceRepeatability was acceptable only during the second week of testing and measures changed with repeated testing and increased with increasing piglet weight, indicating that time (age) and animal body weight should be taken into account when measuring mechanical (nociceptive) thresholds in piglets. Mechanical (nociceptive) thresholds can be used both for testing the efficacy of anaesthetics and analgesics, and for assessing hyperalgesia in chronic pain states in research and clinical settings

Application of long-term cultured interferon-γ enzyme-linked immunospot assay for assessing effector and memory T cell responses in cattle

doi:10.3791/52833 (2015). Effector and memory T cells are generated through developmental programing of naïve cells following antigen recognition. If the infection is controlled up to 95 % of the T cells generated during the expansion phase are eliminated (i.e., contraction phase) and memory T cells remain, sometimes for a lifetime. In humans, two functionally distinct subsets of memory T cells have been described based on the expression of lymph node homing receptors. Central memory T cells express C-C chemokine receptor 7 and CD45RO and are mainly located in T-cell areas of secondary lymphoid organs. Effector memory T cells express CD45RO, lack CCR7 and display receptors associated with lymphocyte homing to peripheral or inflamed tissues. Effector T cells do not express either CCR7 or CD45RO but upon encounter with antigen produce effector cytokines, such as interferon-γ. Interferon-γ release assays are used for the diagnosis of bovine and human tuberculosis and detect primaril

Revisiting the S-matrix approach to the open superstring low energy effective lagrangian

The conventional S-matrix approach to the (tree level) open string low energy effective lagrangian assumes that, in order to obtain all its bosonic ${\alpha'}^N$ order terms, it is necessary to know the open string (tree level) $(N+2)$-point amplitude of massless bosons, at least expanded at that order in $\alpha'$. In this work we clarify that the previous claim is indeed valid for the bosonic open string, but for the supersymmetric one the situation is much more better than that: there are constraints in the kinematical bosonic terms of the amplitude (probably due to Spacetime Supersymmetry) such that a much lower open superstring $n$-point amplitude is needed to find all the ${\alpha'}^N$ order terms. In this `revisited' S-matrix approach we have checked that, at least up to ${\alpha'}^4$ order, using these kinematical constraints and only the known open superstring 4-point amplitude, it is possible to determine all the bosonic terms of the low energy effective lagrangian. The sort of results that we obtain seem to agree completely with the ones achieved by the method of BPS configurations, proposed about ten years ago. By means of the KLT relations, our results can be mapped to the NS-NS sector of the low energy effective lagrangian of the type II string theories implying that there one can also find kinematical constraints in the $N$-point amplitudes and that important informations can be inferred, at least up to ${\alpha'}^4$ order, by only using the (tree level) 4-point amplitude.Comment: 34 pages, 3 figure, Submitted on Aug 4, 2012, Published on Oct 15, 201

Mapping the cellular landscape of Atlantic salmon head kidney by single cell and single nucleus transcriptomics

Single-cell transcriptomics is the current gold standard for global gene expression profiling, not only in mammals and model species, but also in non-model fish species. This is a rapidly expanding field, creating a deeper understanding of tissue heterogeneity and the distinct functions of individual cells, making it possible to explore the complexities of immunology and gene expression on a highly resolved level. In this study, we compared two single cell transcriptomic approaches to investigate cellular heterogeneity within the head kidney of healthy farmed Atlantic salmon (Salmo salar). We compared 14,149 cell transcriptomes assayed by single cell RNA-seq (scRNA-seq) with 18,067 nuclei transcriptomes captured by single nucleus RNA-Seq (snRNA-seq). Both approaches detected eight major cell populations in common: granulocytes, heamatopoietic stem cells, erythrocytes, mononuclear phagocytes, thrombocytes, B cells, NK-like cells, and T cells. Four additional cell types, endothelial, epithelial, interrenal, and mesenchymal cells, were detected in the snRNA-seq dataset, but appeared to be lost during preparation of the single cell suspension submitted for scRNA-seq library generation. We identified additional heterogeneity and subpopulations within the B cells, T cells, and endothelial cells, and revealed developmental trajectories of heamatopoietic stem cells into differentiated granulocyte and mononuclear phagocyte populations. Gene expression profiles of B cell subtypes revealed distinct IgM and IgT-skewed resting B cell lineages and provided insights into the regulation of B cell lymphopoiesis. The analysis revealed eleven T cell sub-populations, displaying a level of T cell heterogeneity in salmon head kidney comparable to that observed in mammals, including distinct subsets of cd4/cd8-negative T cells, such as tcrγ positive, progenitor-like, and cytotoxic cells. Although snRNA-seq and scRNA-seq were both useful to resolve cell type-specific expression in the Atlantic salmon head kidney, the snRNA-seq pipeline was overall more robust in identifying several cell types and subpopulations. While scRNA-seq displayed higher levels of ribosomal and mitochondrial genes, snRNA-seq captured more transcription factor genes. However, only scRNA-seq-generated data was useful for cell trajectory inference within the myeloid lineage. In conclusion, this study systematically outlines the relative merits of scRNA-seq and snRNA-seq in Atlantic salmon, enhances understanding of teleost immune cell lineages, and provides a comprehensive list of markers for identifying major cell populations in the head kidney with significant immune relevance.</p