7 research outputs found
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
The Role of Bacteria-Mitochondria Communication in the Activation of Neuronal Innate Immunity: Implications to Parkinson's Disease
Mitochondria play a key role in regulating host metabolism, immunity and cellular homeostasis. Remarkably, these organelles are proposed to have evolved from an endosymbiotic association between an alphaproteobacterium and a primitive eukaryotic host cell or an archaeon. This crucial event determined that human cell mitochondria share some features with bacteria, namely cardiolipin, N-formyl peptides, mtDNA and transcription factor A, that can act as mitochondrial-derived damage-associated molecular patterns (DAMPs). The impact of extracellular bacteria on the host act largely through the modulation of mitochondrial activities, and often mitochondria are themselves immunogenic organelles that can trigger protective mechanisms through DAMPs mobilization. In this work, we demonstrate that mesencephalic neurons exposed to an environmental alphaproteobacterium activate innate immunity through toll-like receptor 4 and Nod-like receptor 3. Moreover, we show that mesencephalic neurons increase the expression and aggregation of alpha-synuclein that interacts with mitochondria, leading to their dysfunction. Mitochondrial dynamic alterations also affect mitophagy which favors a positive feedback loop on innate immunity signaling. Our results help to elucidate how bacteria and neuronal mitochondria interact and trigger neuronal damage and neuroinflammation and allow us to discuss the role of bacterial-derived pathogen-associated molecular patterns (PAMPs) in Parkinson's disease etiology
Microbial BMAA elicits mitochondrial dysfunction, innate immunity activation, and Alzheimer's disease features in cortical neurons
Background: After decades of research recognizing it as a complex multifactorial disorder, sporadic Alzheimer’s
disease (sAD) still has no known etiology. Adding to the myriad of different pathways involved, bacterial
neurotoxins are assuming greater importance in the etiology and/or progression of sAD. β-N-Methylamino-L-alanine
(BMAA), a neurotoxin produced by some microorganisms namely cyanobacteria, was previously detected in the
brains of AD patients. Indeed, the consumption of BMAA-enriched foods has been proposed to induce
amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), which implicated this microbial metabolite
in neurodegeneration mechanisms.
Methods: Freshly isolated mitochondria from C57BL/6 mice were treated with BMAA and O2 consumption rates
were determined. O2 consumption and glycolysis rates were also measured in mouse primary cortical neuronal
cultures. Further, mitochondrial membrane potential and ROS production were evaluated by fluorimetry and the
integrity of mitochondrial network was examined by immunofluorescence. Finally, the ability of BMAA to activate
neuronal innate immunity was quantified by addressing TLRs (Toll-like receptors) expression, p65 NF-κB
translocation into the nucleus, increased expression of NLRP3 (Nod-like receptor 3), and pro-IL-1β. Caspase-1 activity
was evaluated using a colorimetric substrate and mature IL-1β levels were also determined by ELISA.
Results: Treatment with BMAA reduced O2 consumption rates in both isolated mitochondria and in primary
cortical cultures, with additional reduced glycolytic rates, decrease mitochondrial potential and increased ROS
production. The mitochondrial network was found to be fragmented, which resulted in cardiolipin exposure that
stimulated inflammasome NLRP3, reinforced by decreased mitochondrial turnover, as indicated by increased p62
levels. BMAA treatment also activated neuronal extracellular TLR4 and intracellular TLR3, inducing p65 NF-κB
translocation into the nucleus and activating the transcription of NLRP3 and pro-IL-1β. Increased caspase-1 activity
resulted in elevated levels of mature IL-1β. These alterations in mitochondrial metabolism and inflammation
increased Tau phosphorylation and Aβ peptides production, two hallmarks of AD.
Conclusions: Here we propose a unifying mechanism for AD neurodegeneration in which a microbial toxin can
induce mitochondrial dysfunction and activate neuronal innate immunity, which ultimately results in Tau and Aβ
pathology. Our data show that neurons, alone, can mount inflammatory responses, a role previously attributed
exclusively to glial cells
Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria
Objective Idiopathic Parkinson’s disease (PD) is
characterised by alpha-synuclein
(aSyn) aggregation
and death of dopaminergic neurons in the midbrain.
Recent evidence posits that PD may initiate in the gut
by microbes or their toxins that promote chronic gut
inflammation that will ultimately impact the brain. In this
work, we sought to demonstrate that the effects of the
microbial toxin β-N-
methylamino-
L-
alanine
(BMAA) in
the gut may trigger some PD cases, which is especially
worrying as this toxin is present in certain foods but not
routinely monitored by public health authorities.
Design To test the hypothesis, we treated wild-type
mice, primary neuronal cultures, cell lines and isolated
mitochondria with BMAA, and analysed its impact on gut
microbiota composition, barrier permeability, inflammation
and aSyn aggregation as well as in brain inflammation,
dopaminergic neuronal loss and motor behaviour. To further
examine the key role of mitochondria, we also determined
the specific effects of BMAA on mitochondrial function and
on inflammasome activation.
Results BMAA induced extensive depletion of
segmented filamentous bacteria (SFB) that regulate
gut immunity, thus triggering gut dysbiosis, immune
cell migration, increased intestinal inflammation, loss
of barrier integrity and caudo-rostral
progression of
aSyn. Additionally, BMAA induced in vitro and in vivo
mitochondrial dysfunction with cardiolipin exposure
and consequent activation of neuronal innate immunity.
These events primed neuroinflammation, dopaminergic
neuronal loss and motor deficits.
Conclusion Taken together, our results demonstrate
that chronic exposure to dietary BMAA can trigger a
chain of events that recapitulate the evolution of the PD
pathology from the gut to the brain, which is consistent
with ’gut-first’
PD
Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria
Idiopathic Parkinson's disease (PD) is characterised by alpha-synuclein (aSyn) aggregation and death of dopaminergic neurons in the midbrain. Recent evidence posits that PD may initiate in the gut by microbes or their toxins that promote chronic gut inflammation that will ultimately impact the brain. In this work, we sought to demonstrate that the effects of the microbial toxin β-N-methylamino-L-alanine (BMAA) in the gut may trigger some PD cases, which is especially worrying as this toxin is present in certain foods but not routinely monitored by public health authorities.This work was funded by Santa Casa da Misericórdia de Lisboa, Portugal, through Mantero Belard Neurosciences Prize 2016 (MB-40-2016); by FMUCPEPITA (2018); by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01-0145-FEDER-000012 (HealthyAging 2020) and through the COMPETE 2020 - Operational
Programme for Competitiveness and Internationalization and by Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia under projects PTDC/MED-NEU/3644/2020, PINFRA/22184/2016/POCI-01-0145-FEDER-022184 and UIDB/04539/2020. EC was supported by fellowship MB-40-2016. IT was supported by IF/01061/2014 Investigator contract. JDM is supported by PhD fellowship PD/BD/146409/2019, DN-C is supported by PhD fellowship SFRH/B
Characterisation of microbial attack on archaeological bone
As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved