Neuronal differentiation in the adult hippocampus recapitulates embryonic development

In the adult hippocampus and olfactory bulb, neural progenitor cells generate neurons that functionally integrate into the existing circuits. To understand how neuronal differentiation occurs in the adult hippocampus, we labeled dividing progenitor cells with a retrovirus expressing green fluorescent protein and studied the morphological and functional properties of their neuronal progeny over the following weeks. During the first week neurons had an irregular shape and immature spikes and were synaptically silent. Slow GABAergic synaptic inputs first appeared during the second week, when neurons exhibited spineless dendrites and migrated into the granule cell layer. In contrast, glutamatergic afferents were detected by the fourth week in neurons displaying mature excitability and morphology. Interestingly, fast GABAergic responses were the latest to appear. It is striking that neuronal maturation in the adult hippocampus follows a precise sequence of connectivity (silent → slow GABA → glutamate → fast GABA) that resembles hippocampal development. We conclude that, unlike what is observed in the olfactory bulb, the hippocampus maintains the same developmental rules for neuronal integration through adulthood.Fil: Esposito, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Piatti, Veronica del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Laplagne, Diego Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Morgenstern, Nicolás Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ferrari, Carina Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Pitossi, Fernando Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Schinder, Alejandro Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Aislamiento comunitario como estrategias para la mitigación de un brote de COVID19: el caso de Villa Azul

Introduction: After the identification of the occurrence of a COVID19 outbreak in the Villa Azul neighborhood and given the neighborhood's vulnerability characteristics that would make it difficult to comply with quarantine and prevention measures, a community isolation strategy was implemented as a health response to the outbreak. Objective: to describe the community isolation strategy used in the Villa Azul neighborhood to contain and mitigate a COVID19 outbreak.Methods: The boundaries of the neighborhood were closed with security forces. Circulation within the neighborhood was allowed assuming that all the inhabitants were suspected cases of COVID19 or were close contacts of a case. In the following days, the active search for suspected cases of COVID19 continued, swabs were carried out in the neighborhood and the results were obtained at 24 hours. Every day, after receiving the cases, the negative cases were informed of the result and the positive cases went to the houses to notify them of the result and suggest isolation outside the neighborhood to cut the chain of infectionsResults: In the Villa Azul neighborhood, between May 22 and June 20, 731 suspected cases were registered, of which 379 were confirmed cases for COVID19 (accumulated positivity rate of 52.1%). The first week there were between 20 and 40 confirmed daily cases with a positivity rate between 66 and 81%, but as time went by as a consequence of the strategy described, the number of cases per day and also the positivity decreased. 193 confirmed patient transfers were transferred to isolate themselves outside the neighborhood. 3 people died, all with comorbidities (letality rate 0.8%).Discussion: The community isolation strategy was effective in containing the COVID19 outbreak in the Villa Azul neighborhood. The possibility of guaranteeing the active search for cases on a daily basis, added to the possibility of swabbing them in the neighborhood and having the result after 24 hours plus suggesting the transfer out of the same of those confirmed for COVID19 were some of the keys.Introducción: frente a la identificación de la ocurrencia de un brote de COVID19 en el Barrio de Villa Azul y dadas las características de vulnerabilidad del barrio que dificultarían cumplir con el aislamiento domiciliario y las medidas de prevención se implementó una estrategia de aislamiento comunitario como respuesta sanitaria al brote.    Objetivo: describir la estrategia de aislamiento comunitario utilizada en el Barrio de Villa Azul para contener y mitigar un brote de COVID19. Métodos: Se identificaron los límites del barrio y se procedió al cierre del mismo con fuerzas de seguridad. Quedó permitida la circulación por dentro del barrio asumiendo que todos los habitantes eran casos sospechosos de COVID19 o bien eran contactos estrechos de algún caso. En los días subsiguientes se continuó con la búsqueda activa de casos sospechosos de COVID19, se realizaron los hisopados en el barrio y se obtuvieron los resultados a las 24 horas. Todos los días, luego de la recepción de los casos se les informaba el resultado a los casos negativos y se iba a las casas de los casos positivos para notificarlos del resultado y sugerirles el aislamiento fuera del barrio para cortar la cadena de contagios. Resultados: En el barrio Villa Azul entre el 22 de mayo y el 20 de junio se registraron 731 casos sospechosos de los cuales 379 fueron casos confirmados para COVID19 (tasa de positividad acumulada del 52,1%). La primera semana hubo entre 20 y 40 casos confirmados diarios con un índice de positividad entre el 66 y 81% pero con el correr del tiempo como consecuencia de la estrategia descripta fueron bajando el número de casos por día y también la positividad. Se trasladaron 193 traslados de pacientes confirmados para aislarse afuera del barrio. Fallecieron 3 personas, todas con comorbilidades (tasa de letalidad 0,8%).  Discusión: La estrategia de aislamiento comunitario resultó efectiva para contener el brote de COVID19 en el Barrio de Villa Azul. La posibilidad de garantizar de forma diaria la búsqueda activa de casos, sumado a la posibilidad de hisoparlos en el barrio y a las 24 horas tener el resultado, sugiriendo luego el traslado fuera del mismo de los confirmados para COVID19 fueron algunas de las claves

Locomotor speed control circuits in the caudal brainstem

Locomotion is a universal behaviour that provides animals with the ability to move between places. Classical experiments have used electrical microstimulation to identify brain regions that promote locomotion, but the identity of neurons that act as key intermediaries between higher motor planning centres and executive circuits in the spinal cord has remained controversial. Here we show that the mouse caudal brainstem encompasses functionally heterogeneous neuronal subpopulations that have differential effects on locomotion. These subpopulations are distinguishable by location, neurotransmitter identity and connectivity. Notably, glutamatergic neurons within the lateral paragigantocellular nucleus (LPGi), a small subregion in the caudal brainstem, are essential to support high-speed locomotion, and can positively tune locomotor speed through inputs from glutamatergic neurons of the upstream midbrain locomotor region. By contrast, glycinergic inhibitory neurons can induce different forms of behavioural arrest mapping onto distinct caudal brainstem regions. Anatomically, descending pathways of glutamatergic and glycinergic LPGi subpopulations communicate with distinct effector circuits in the spinal cord. Our results reveal that behaviourally opposing locomotor functions in the caudal brainstem were historically masked by the unexposed diversity of intermingled neuronal subpopulations. We demonstrate how specific brainstem neuron populations represent essential substrates to implement key parameters in the execution of motor programs

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Brainstem nucleus MdV mediates skilled forelimb motor tasks

Translating the behavioural output of the nervous system into movement involves interaction between brain and spinal cord. The brainstem provides an essential bridge between the two structures, but circuit-level organization and function of this intermediary system remain poorly understood. Here we use intersectional virus tracing and genetic strategies in mice to reveal a selective synaptic connectivity matrix between brainstem substructures and functionally distinct spinal motor neurons that regulate limb movement. The brainstem nucleus medullary reticular formation ventral part (MdV) stands out as specifically targeting subpopulations of forelimb-innervating motor neurons. Its glutamatergic premotor neurons receive synaptic input from key upper motor centres and are recruited during motor tasks. Selective neuronal ablation or silencing experiments reveal that MdV is critically important specifically for skilled motor behaviour, including accelerating rotarod and single-food-pellet reaching tasks. Our results indicate that distinct premotor brainstem nuclei access spinal subcircuits to mediate task-specific aspects of motor programs

Motor-circuit communication matrix from spinal cord to brainstem neurons revealed by developmental origin

Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement