283 research outputs found

    Waterhouse Friderichsen Syndrome: Medico-legal issues

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    The Waterhouse-Friderichsen Syndrome (WFS) is a pediatric emergency characterized by high mortality due to the combination of bilateral adrenal haemorrhage, meningococcal infection and cutaneous purpura. WFS often raises medico-legal problems related to missed or delayed diagnosis mainly related to the short clinical course, the sudden onset of symptoms and unexpected death. We report the death of a 2-year-old child who had no other pathologies. Death occurred quickly about 20 h after the first care visit. The forensic autopsy was ordered following the parental complaint for diagnostic delay in primary care. Clinical data, autopsy and histological findings were consistent for WFS by Neisseria meningitidis (NM) serotype B. Medical malpractice was excluded. WFS has a rapid clinical course. By the time fever and purpura are reported, it may be too late as thrombotic and bleeding complications may already be present

    The effects of reduced physical activity on the lipid profile in patients with high cardiovascular risk during covid-19 lockdown

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    Background: The COVID-19 pandemic is a serious global health problem. In Italy, to limit the infections, the government ordered lockdown from March 2020. This measure, designed to contain the virus, led to serious limitations on the daily life of the individuals it affected, and in particular in the limitation of physical exercise. The aim of this study was to evaluate the effects of reduced physical activity on the lipid profile in patients with high cardiovascular risk. Methods: We enrolled 38 dyslipidemic patients, 56% male, with an age range of 44–62 years, considered to be at high cardiovascular risk. All patients were prescribed statin drug therapy (atorvastatin 40 mg) and a vigorous physical activity program four times a week, 1 h per session. In addition, a personalized Mediterranean diet was prescribed to all the patients. Total cholesterol, LDL, HDL and triglycerides were measured in patients at T0 before lockdown and at T1 during lockdown. Results: Data showed a significant increase (p < 0.01) in total cholesterol (+6,8%) and LDL (+15,8%). Furthermore, the analysis of the data revealed a reduction in HDL (−3%) and an increase in triglycerides (+3,2%), although both were not significant (p > 0.05). Conclusions: Our study showed that the reduction in physical activity during lockdown led to an increase in LDL levels, and therefore, in the risk of ischemic heart disease in dyslipidemic patients with high cardiovascular risk

    Azithromycin Drives Alternative Macrophage Activation and Improves Recovery and Tissue Sparing in Contusion Spinal Cord Injury

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    BACKGROUND: Macrophages persist indefinitely at sites of spinal cord injury (SCI) and contribute to both pathological and reparative processes. While the alternative, anti-inflammatory (M2) phenotype is believed to promote cell protection, regeneration, and plasticity, pro-inflammatory (M1) macrophages persist after SCI and contribute to protracted cell and tissue loss. Thus, identifying non-invasive, clinically viable, pharmacological therapies for altering macrophage phenotype is a challenging, yet promising, approach for treating SCI. Azithromycin (AZM), a commonly used macrolide antibiotic, drives anti-inflammatory macrophage activation in rodent models of inflammation and in humans with cystic fibrosis. METHODS: We hypothesized that AZM treatment can alter the macrophage response to SCI and reduce progressive tissue pathology. To test this hypothesis, mice (C57BL/6J, 3-month-old) received daily doses of AZM (160 mg/kg) or vehicle treatment via oral gavage for 3 days prior and up to 7 days after a moderate-severe thoracic contusion SCI (75-kdyn force injury). Fluorescent-activated cell sorting was used in combination with real-time PCR (rtPCR) to evaluate the disposition and activation status of microglia, monocytes, and neutrophils, as well as macrophage phenotype in response to AZM treatment. An open-field locomotor rating scale (Basso Mouse Scale) and gridwalk task were used to determine the effects of AZM treatment on SCI recovery. Bone marrow-derived macrophages (BMDMs) were used to determine the effect of AZM treatment on macrophage phenotype in vitro. RESULTS: In accordance with our hypothesis, SCI mice exhibited significantly increased anti-inflammatory and decreased pro-inflammatory macrophage activation in response to AZM treatment. In addition, AZM treatment led to improved tissue sparing and recovery of gross and coordinated locomotor function. Furthermore, AZM treatment altered macrophage phenotype in vitro and lowered the neurotoxic potential of pro-inflammatory, M1 macrophages. CONCLUSIONS: Taken together, these data suggest that pharmacologically intervening with AZM can alter SCI macrophage polarization toward a beneficial phenotype that, in turn, may potentially limit secondary injury processes. Given that pro-inflammatory macrophage activation is a hallmark of many neurological pathologies and that AZM is non-invasive and clinically viable, these data highlight a novel approach for treating SCI and other maladaptive neuroinflammatory conditions

    Lumped Parameter Models of the Central Nervous System for VIIP Research

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    INTRODUCTION: Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit, such as to Mars and asteroids, expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome [1]. It has been hypothesized that the headward shift of cerebral spinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn induces VIIP syndrome through biomechanical pathways [1, 2]. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the realted IWS abstracts submitted by Nelson et al., Feola et al. and Ethier et al. METHODS: We have developed a nine compartment CNS model (Figure 1) capable of both time-dependent and steady state fluid transport simulations, based on the works of Stevens et al. [3]. The breakdown of compartments within the model includes: vascular (3), CSF (2), brain (1) and extracranial (3). The boundary pressure in the Central Arteries [A] node is prescribed using an oscillating pressure function PA(t) simulating the carotid pulsatile pressure wave as developed by Linninger et al. [4]. For each time step, pressures are integrated through time using an adaptive-timestep 4th and 5th order Runga-Kutta solver. Once pressures are found, constitutive equations are used to solve for flowrates (Q) between each compartment. In addition to fluid flow between the different compartments, compliance (C) interactions between neighboring compartments are represented. We are also developing a second CNS model based on the works of Linninger et al. [4] which takes a more granular approach to represent the interactions of the intracranial and spinal compartments with the inclusion of arteries, arterioles, capillaries, venules, veins, venous sinus, and ventricles. The flow through the arteries, veins and CSF compartments are governed by continuity, momentum and distensibility balance equations. Furthermore, unlike the Stevens et al. approach, the Monro-Kellie doctrine of constant cranial volume and the bi-phasic nature of the brain parenchyma are implemented. These features appear to be more consistent with the physiologic and anatomical behavior of the CNS, and follow a modeling philosophy similar to the lumped parameter eye model that is intended to be integrated with the CNS model. However, Linningers approach has never been implemented to include hydrostatic gradient and microgravity simulation capabilities. Therefore, we aim at implement this modeling approach for spaceflight simulations and assess its overall applicability to VIIP research. OBJECTIVES: We will present verification and validation test results for both models, as well as head-to-head comparison to explore their strengths and limitations with respect to mathematical implementation and physiological significance for VIIP research. In doing so, we hope to provide some guidance to the HRP research community on how to appropriately leverage lumped parameter models for space biomedical research

    Numerical Modeling of Ophthalmic Response to Space

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    To investigate ophthalmic changes in spaceflight, we would like to predict the impact of blood dysregulation and elevated intracranial pressure (ICP) on Intraocular Pressure (IOP). Unlike other physiological systems, there are very few lumped parameter models of the eye. The eye model described here is novel in its inclusion of the human choroid and retrobulbar subarachnoid space (rSAS), which are key elements in investigating the impact of increased ICP and ocular blood volume. Some ingenuity was required in modeling the blood and rSAS compartments due to the lack of quantitative data on essential hydrodynamic quantities, such as net choroidal volume and blood flowrate, inlet and exit pressures, and material properties, such as compliances between compartments

    Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-β Associated Neurodegenerative Pathways and Glial Signatures in a Mouse Model of Alzheimer’s Disease: A Targeted Transcriptome Analysis

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    Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, it remains unclear how Arg1 deficiency in these cells impacts the whole brain to promote amyloidosis. Herein, we aim to determine how Arg1 deficiency driven by LysM restriction during amyloidosis affects fundamental neurodegenerative pathways at the transcriptome level. By applying several bioinformatic tools and analyses, we found that amyloid-β (Aβ) stimulated transcriptomic signatures in autophagy-related pathways and myeloid cells’ inflammatory response. At the same time, myeloid Arg1 deficiency during amyloidosis promoted gene signatures of lipid metabolism, myelination, and migration of myeloid cells. Focusing on Aβ associated glial transcriptomic signatures, we found myeloid Arg1 deficiency up-regulated glial gene transcripts that positively correlated with Aβ plaque burden. We also observed that Aβ preferentially activated disease-associated microglial signatures to increase phagocytic response, whereas myeloid Arg1 deficiency selectively promoted homeostatic microglial signature that is non-phagocytic. These transcriptomic findings suggest a critical role for proper Arg1 function during normal and pathological challenges associated with amyloidosis. Furthermore, understanding pathways that govern Arg1 metabolism may provide new therapeutic opportunities to rebalance immune function and improve microglia/macrophage fitness

    Conservation actions for restoring the coastal lagoon habitats: Strategy and multidisciplinary approach of LIFE Lagoon Refresh

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    The Habitat Directive of European Union lists Costal Lagoons (habitat code 1150*) among priority habitats because they are in danger of disappearance. Natural ecosystems may recover from anthropogenic perturbations; however, the recovery can follow natural restoration or it can be redirected through ecological restoration by anthropogenic intervention. Accordingly, by collecting the available theoretical indications for restoration of estuarine and coastal areas, a methodological approach was detailed andit can be summarised into five issues: (i) Environmental context from which it began; (ii) Desired state to be achieved; (iii) Policies and socio-economic context; (iv) Typology of recovery and/or improvement of habitats and ecosystems; and (v) Methods for monitoring the impact of the project. The project strategy, management and measures of LIFE Lagoon Refresh were also presented and discussed, as a case study for the implementation of the multidisciplinary approach for restoration ecology in transitional waters. The project takes place in the northern Venice Lagoon (Italy), started in 2017 and it lasts 5 years. In the Venice Lagoon, since the 20th century, strong reductions of the typical salinity gradient of buffer areas between lagoon and mainland, and of reedbed extensions have occurred due to historic human interventions, with negative consequences on coastal lagoon habitats. To improve the conservation status of habitats and biodiversity of the area, the LIFE Lagoon Refresh project included several conservative actions, which are (i) the diversion of a freshwater flow from the Sile River into the lagoon; (ii) the restoration of intertidal morphology, through biodegradable structures; (iii) the reed and aquatic angiosperm transplantations with the involvement of local fishermen and hunters, and (iv) the reduction of hunting and fishing pressures in the intervention area. To achieve the restoration of the lagoon environment, the strategy of the project covered a combination of different aspects and tools, such as planning activities, through the involvement of local Institutions and communities; stakeholder's involvement to increase awareness of environment conservation and socioeconomic value improvement; an ecological engineering approach; numerical models as supporting tool for planning and managing of conservation actions; environmental monitoring performed before and after the conservation actions

    Conservation actions for restoring the coastal lagoon habitats: Strategy and multidisciplinary approach of LIFE Lagoon Refresh

    Get PDF
    The Habitat Directive of European Union lists Costal Lagoons (habitat code 1150*) among priority habitats because they are in danger of disappearance. Natural ecosystems may recover from anthropogenic perturbations; however, the recovery can follow natural restoration or it can be redirected through ecological restoration by anthropogenic intervention. Accordingly, by collecting the available theoretical indications for restoration of estuarine and coastal areas, a methodological approach was detailed andit can be summarised into five issues: (i) Environmental context from which it began; (ii) Desired state to be achieved; (iii) Policies and socio-economic context; (iv) Typology of recovery and/or improvement of habitats and ecosystems; and (v) Methods for monitoring the impact of the project. The project strategy, management and measures of LIFE Lagoon Refresh were also presented and discussed, as a case study for the implementation of the multidisciplinary approach for restoration ecology in transitional waters. The project takes place in the northern Venice Lagoon (Italy), started in 2017 and it lasts 5 years. In the Venice Lagoon, since the 20th century, strong reductions of the typical salinity gradient of buffer areas between lagoon and mainland, and of reedbed extensions have occurred due to historic human interventions, with negative consequences on coastal lagoon habitats. To improve the conservation status of habitats and biodiversity of the area, the LIFE Lagoon Refresh project included several conservative actions, which are (i) the diversion of a freshwater flow from the Sile River into the lagoon; (ii) the restoration of intertidal morphology, through biodegradable structures; (iii) the reed and aquatic angiosperm transplantations with the involvement of local fishermen and hunters, and (iv) the reduction of hunting and fishing pressures in the intervention area. To achieve the restoration of the lagoon environment, the strategy of the project covered a combination of different aspects and tools, such as planning activities, through the involvement of local Institutions and communities; stakeholder’s involvement to increase awareness of environment conservation and socioeconomic value improvement; an ecological engineering approach; numerical models as supporting tool for planning and managing of conservation actions; environmental monitoring performed before and after the conservation actions
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