Sensorimotor pathway controlling stopping behavior during chemotaxis in the Drosophila melanogaster larva.

Sensory navigation results from coordinated transitions between distinct behavioral programs. During chemotaxis in the Drosophila melanogaster larva, the detection of positive odor gradients extends runs while negative gradients promote stops and turns. This algorithm represents a foundation for the control of sensory navigation across phyla. In the present work, we identified an olfactory descending neuron, PDM-DN, which plays a pivotal role in the organization of stops and turns in response to the detection of graded changes in odor concentrations. Artificial activation of this descending neuron induces deterministic stops followed by the initiation of turning maneuvers through head casts. Using electron microscopy, we reconstructed the main pathway that connects the PDM-DN neuron to the peripheral olfactory system and to the pre-motor circuit responsible for the actuation of forward peristalsis. Our results set the stage for a detailed mechanistic analysis of the sensorimotor conversion of graded olfactory inputs into action selection to perform goal-oriented navigation

Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders

Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The wiring diagram of antennal lobe and mapping a brain circuit that controls chemotaxis behavior in the Drosophila larva

Drosophila larvae present unique opportunity for anatomical and functional mapping of their nervous system because of features such as numerical simplicity of neurons its nervous system is composed of, and ability to exhibit quantifiable behaviors such as chemotaxis. Here, we mapped entire antennal lobe of larval Drosophila with one of its circuits responsible for controlling sensorimotor transformation in lateral horn (LH) (higher brain) through a single brain descending neuron using electron microscopic 3D reconstruction. In antennal lobe, we reported a canonical circuit with uniglomerular projection neurons (uPNs), working to relay gain-controlled ORN activity to higher brain centers like Mushroom body and lateral horn. We also found a parallel circuit with multiglomerular projection neurons (mPNs) and hierarchically organized local neurons (LNs) selectively integrating signal from multiple ORNs at the first synapse with LN-LN connectivity putatively implementing gain control mechanism that can potentially switch from computing distinguished odor signals through panglomerular inhibition to allowing system to respond to faint aversive odor in an environment rich with strong appetitive odors. We also reconstructed and studied one of the olfactory connected circuits in the LH that was found to be influencing chemotaxis behavior in larva through a single brain descending neuron, PVM027. We found that this neuron was responsible in controlling stop response of chemotaxis behavior. EM reconstruction revealed its connection with variety of motor systems and SEZ descending neurons in the VNC. Connections were revealed with the peristaltic wave propagation circuit of larva, and PVM027 was found to be implementing stop by terminating and ceasing the origin of forward peristaltic waves.Las larvas de Drosophila ofrecen una oportunidad única para el mapeo anatómico y funcional de su sistema nervioso debido a propiedades como la simplicidad numérica de neuronas que componen su sistema nervioso y su habilidad de exhibir comportamientos cuantificables como la quimiotaxis. En este estudio hemos mapeado el lóbulo antenal de la larva de Drosophila con uno de sus circuitos responsable de controlar la transformación sensorial-motora en el asta lateral (LH) (cerebro superior) a través de una sola neurona descendiente usando la reconstrucción 3D para microscopia electrónica. Hemos presentado, en el lóbulo antenal, un circuito canónico con proyecciones neuronales uniglomerulares (uPNs) responsables de transmitir aumentos controlados de actividad desde sus ORN* hasta centros superiores del cerebro como el cuerpo fungiforme y el asta lateral del protocerebro. Hemos descubierto también un circuito paralelo formado por neuronas con proyecciones multiglomerulares (mPNs) y neuronas locales (Lns), organizadas jerárquicamente, que integran selectivamente señales desde múltiples ORNs a nivel de primera sinapsis con conectividad LN-LN implementando aparentemente un mecanismo de aumento de control que potencialmente puede intercambiar señales olfativas distintas computacionalmente a través de inhibición panglomerular permitiendo al sistema responder a olores vagamente aversivos en un ambiente rico en fuertes olores apetitosos. También hemos reconstruido y estudiado uno de los circuitos olfativos que conectan con el LH conocido por influenciar la quimiotaxis de la larva a través de un sola neurona cerebral descendiente, la PVM027. Hemos descubierto que dicha neurona es la responsable de controlar la respuesta stop en el comportamiento de quimiotaxis. La reconstrucción por EM revela su conexión con una variedad de sistemas motores así como neuronas descendientes SEZ en el VNC. Observamos dichas conexiones gracias al circuito de propagación de onda peristáltica de la larva, y descubrimos que la PVM027 implementa la señal de stop terminando e interrumpiendo el origen de la onda peristáltica

Genital self-mutilation in a case of first episode psychosis

Genital self-mutilation (GSM) is a much rare finding and more commonly associated with psychosis when it comes to comparison with self-mutilation as a whole. There have been anecdotal case reports of GSM in psychotic disorders with most of them being in long standing psychoses. We describe herein a case of GSM during the first episode of psychosis where multiple phenomenological variables were seen responsible for the act

Computed Tomography Coronary Angiography for Evaluation of Children With Kawasaki Disease.

We sought to assess the feasibility of computed tomography coronary angiography (CTCA) on a 128-slice, dual source scanner in children with acute and convalescent phase Kawasaki disease (KD).A prospective study of 49 children with KD (12 at presentation and 37 in the convalescent phase) was conducted between November 2013 and April 2015. CTCA was performed with either prospective (n = 37) or retrospective (n = 12) electrocardiographic gating. A radiologist blinded to clinical profile and echocardiogram evaluated each scan.Median age (36 boys and 13 girls) was 7 years. Median dose-length product value and median effective CT radiation dose was 32mGycm (interquartile range [IQR]: 21-74) and 0.54 miliSieverts (mSv) (IQR: 0.77-3.2) for all scans, and 27mGycm (IQR: 18.5-33.75) and 0.48mSv (IQR: 0.18-1.17) for prospectively triggered scans (n = 37). Fourteen subjects (30 coronary segments) showed abnormalities by CTCA including aneurysms (n = 27) and stenoses (n = 3). In the acute phase (n = 12), aneurysms were detected in 5 children (18 segments).CTCA allows comprehensive evaluation of coronary arteries in children with KD

Computed Tomography Coronary Angiography for Evaluation of Children With Kawasaki Disease.

We sought to assess the feasibility of computed tomography coronary angiography (CTCA) on a 128-slice, dual source scanner in children with acute and convalescent phase Kawasaki disease (KD).A prospective study of 49 children with KD (12 at presentation and 37 in the convalescent phase) was conducted between November 2013 and April 2015. CTCA was performed with either prospective (n = 37) or retrospective (n = 12) electrocardiographic gating. A radiologist blinded to clinical profile and echocardiogram evaluated each scan.Median age (36 boys and 13 girls) was 7 years. Median dose-length product value and median effective CT radiation dose was 32mGycm (interquartile range [IQR]: 21-74) and 0.54 miliSieverts (mSv) (IQR: 0.77-3.2) for all scans, and 27mGycm (IQR: 18.5-33.75) and 0.48mSv (IQR: 0.18-1.17) for prospectively triggered scans (n = 37). Fourteen subjects (30 coronary segments) showed abnormalities by CTCA including aneurysms (n = 27) and stenoses (n = 3). In the acute phase (n = 12), aneurysms were detected in 5 children (18 segments).CTCA allows comprehensive evaluation of coronary arteries in children with KD

Influence of loading rate and hydrogen content on fracture toughness of Zr-2.5Nb pressure tube material

For the safety assessment of PHWR, it is required to study the flaw tolerance capacity of the pressure tubes as a function of the loading rate. In this work, the effect of loading rate and hydrogen content on the fracture behaviour of a Zr-2.5Nb alloy pressure tube was investigated between 25 and 300 degrees C. For the as received material, the pulling rate only had an effect on fracture toughness at 25 degrees C whereas for. hydrided material the pulling rate affected fracture toughness in the transition regime. For all pulling rates, hydrided materials showed typical S curve behavior with an increase in lower shelf, upper shelf and transition temperature with pulling rate. The number of axial splits on fracture surfaces increased with an increase in the pulling rate and a decrease in temperature and fracture toughness was found to decrease with an increase in the number of axial splits. The reduction in fracture toughness is attributed to a localised deformation between axial splits. (C) 2015 Elsevier B.V. All rights reserved

Sensorimotor pathway controlling stopping behavior during chemotaxis in the Drosophila melanogaster larva

Sensory navigation results from coordinated transitions between distinct behavioral programs. During chemotaxis in the Drosophila melanogaster larva, the detection of positive odor gradients extends runs while negative gradients promote stops and turns. This algorithm represents a foundation for the control of sensory navigation across phyla. In the present work, we identified an olfactory descending neuron, PDM-DN, which plays a pivotal role in the organization of stops and turns in response to the detection of graded changes in odor concentrations. Artificial activation of this descending neuron induces deterministic stops followed by the initiation of turning maneuvers through head casts. Using electron microscopy, we reconstructed the main pathway that connects the PDM-DN neuron to the peripheral olfactory system and to the pre-motor circuit responsible for the actuation of forward peristalsis. Our results set the stage for a detailed mechanistic analysis of the sensorimotor conversion of graded olfactory inputs into action selection to perform goal-oriented navigation.This work was initiated as part of the multi-lab Larval Olympiad conducted at the Janelia Research Campus. We are in debt to the work of S Reid (Louis lab) during the initial phase of the screen. We thank I Andrade, A Fushiki, J Jonaitis, I Larderet, P Schegel, C Schneider-Mizell and M Zwart for contributing to the EM reconstruction. We thank H Aberle for glutamate antibodies, as well as V Jayaraman, A Nern, S Pulver, G Rubin and J. Simpson for sharing fly lines. We thank V Jayaraman and R Francoville for training and access to the functional imaging setup. ML and DT acknowledges support of the Spanish Ministry of Economy and Competitiveness (MICINN and BFU2011-26208), ‘Centro de Excelencia Severo Ochoa 2013–2017’, the CERCA Programme/Generalitat de Catalunya, the EMBL/CRG Systems Biology Program and the University of California, Santa Barbara. IT was supported by the Marie Curie FP7 Programme through FLiACT (ITN). AK was supported by the ‘La Caixa’ International PhD Programme. JT, MZ and AC acknowledge funding from the Howard Hughes Medical Institute