High-flow nasal cannula (HFNC) is an emerging therapy for respiratory failure but the extent of exhaled air dispersion during treatment is unknown. We examined exhaled air dispersion during HFNC ...therapy
continuous positive airway pressure (CPAP) on a human patient simulator (HPS) in an isolation room with 16 air changes·h
.
The HPS was programmed to represent different severity of lung injury. CPAP was delivered at 5-20 cmH
O
nasal pillows (Respironics Nuance Pro Gel or ResMed Swift FX) or an oronasal mask (ResMed Quattro Air). HFNC, humidified to 37°C, was delivered at 10-60 L·min
to the HPS. Exhaled airflow was marked with intrapulmonary smoke for visualisation and revealed by laser light-sheet. Normalised exhaled air concentration was estimated from the light scattered by the smoke particles. Significant exposure was defined when there was ≥20% normalised smoke concentration.
In the normal lung condition, mean±sd exhaled air dispersion, along the sagittal plane, increased from 186±34 to 264±27 mm and from 207±11 to 332±34 mm when CPAP was increased from 5 to 20 cmH
O
Respironics and ResMed nasal pillows, respectively. Leakage from the oronasal mask was negligible. Mean±sd exhaled air distances increased from 65±15 to 172±33 mm when HFNC was increased from 10 to 60 L·min
. Air leakage to 620 mm occurred laterally when HFNC and the interface tube became loose.
Exhaled air dispersion during HFNC and CPAP
different interfaces is limited provided there is good mask interface fitting.
BACKGROUND Noninvasive ventilation (NIV) via helmet or total facemask is an option for managing patients with respiratory infections in respiratory failure. However, the risk of nosocomial infection ...is unknown. METHODS We examined exhaled air dispersion during NIV using a human patient simulator reclined at 45° in a negative pressure room with 12 air changes/h by two different helmets via a ventilator and a total facemask via a bilevel positive airway pressure device. Exhaled air was marked by intrapulmonary smoke particles, illuminated by laser light sheet, and captured by a video camera for data analysis. Significant exposure was defined as where there was ≥ 20% of normalized smoke concentration. RESULTS During NIV via a helmet with the simulator programmed in mild lung injury, exhaled air leaked through the neck-helmet interface with a radial distance of 150 to 230 mm when inspiratory positive airway pressure was increased from 12 to 20 cm H2 O, respectively, while keeping the expiratory pressure at 10 cm H2 O. During NIV via a helmet with air cushion around the neck, there was negligible air leakage. During NIV via a total facemask for mild lung injury, air leaked through the exhalation port to 618 and 812 mm when inspiratory pressure was increased from 10 to 18 cm H2 O, respectively, with the expiratory pressure at 5 cm H2 O. CONCLUSIONS A helmet with a good seal around the neck is needed to prevent nosocomial infection during NIV for patients with respiratory infections.
A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by ...transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients' lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1β/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D
, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.
Autophagy is a conserved intracellular degradation process enclosing the bulk of cytosolic components for lysosomal degradation to maintain cellular homeostasis. Accumulating evidences showed that a ...specialized form of autophagy, known as xenophagy, could serve as an innate immune response to defend against pathogens invading inside the host cells. Correspondingly, infectious pathogens have developed a variety of strategies to disarm xenophagy, leading to a prolonged and persistent intracellular colonization. In this review, we first summarize the current knowledge about the general mechanisms of intracellular bacterial infections and xenophagy. We then focus on the ongoing battle between these two processes.
Mask ventilation and coughing during oro-tracheal suctioning produce aerosols that enhance nosocomial transmission of respiratory infections. We examined the extent of exhaled air dispersion from a ...human-patient-simulator during mask ventilation by different groups of healthcare workers and coughing bouts. The simulator was programmed to mimic varying severity of lung injury. Exhaled airflow was marked with tiny smoke particles, and highlighted by laser light-sheet. We determined the normalized exhaled air concentration in the leakage jet plume from the light scattered by smoke particles. Smoke concentration ≥20% was considered as significant exposure. Exhaled air leaked from mask-face interface in the transverse plane was most severe (267 ± 44 mm) with Ambu silicone resuscitator performed by nurses. Dispersion was however similar among anesthesiologists/intensivists, respiratory physicians and medical students using Ambu or Laerdal silicone resuscitator, p = 0.974. The largest dispersion was 860 ± 93 mm during normal coughing effort without tracheal intubation and decreased with worsening coughing efforts. Oro-tracheal suctioning reduced dispersion significantly, p < 0.001, and was more effective when applied continuously. Skills to ensure good fit during mask ventilation are important in preventing air leakage through the mask-face interface. Continuous oro-tracheal suctioning minimized exhaled air dispersion during coughing bouts when performing aerosol-generating procedures.
We compared the expelled air dispersion distances during coughing from a human patient simulator (HPS) lying at 45° with and without wearing a surgical mask or N95 mask in a negative pressure ...isolation room.
Airflow was marked with intrapulmonary smoke. Coughing bouts were generated by short bursts of oxygen flow at 650, 320, and 220L/min to simulate normal, mild and poor coughing efforts, respectively. The coughing jet was revealed by laser light-sheet and images were captured by high definition video. Smoke concentration in the plume was estimated from the light scattered by smoke particles. Significant exposure was arbitrarily defined where there was ≥ 20% of normalized smoke concentration.
During normal cough, expelled air dispersion distances were 68, 30 and 15 cm along the median sagittal plane when the HPS wore no mask, a surgical mask and a N95 mask, respectively. In moderate lung injury, the corresponding air dispersion distances for mild coughing efforts were reduced to 55, 27 and 14 cm, respectively, p < 0.001. The distances were reduced to 30, 24 and 12 cm, respectively during poor coughing effort as in severe lung injury. Lateral dispersion distances during normal cough were 0, 28 and 15 cm when the HPS wore no mask, a surgical mask and a N95 mask, respectively.
Normal cough produced a turbulent jet about 0.7 m towards the end of the bed from the recumbent subject. N95 mask was more effective than surgical mask in preventing expelled air leakage during coughing but there was still significant sideway leakage.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The role of N
6
-methyladenosine (m
6
A) modification of host mRNA during bacterial infection is unclear. Here, we show that
Helicobacter pylori
infection upregulates host m
6
A methylases ...and increases m
6
A levels in gastric epithelial cells. Reducing m
6
A methylase activity via hemizygotic deletion of methylase-encoding gene
Mettl3
in mice, or via small interfering RNAs targeting m
6
A methylases, enhances
H. pylori
colonization. We identify LOX-1 mRNA as a key m
6
A-regulated target during
H. pylori
infection. m
6
A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for
H. pylori
catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of
Lox-1
, reduces
H. pylori
colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of
H. pylori
to human gastric sections. Our results indicate that m
6
A modification of host LOX-1 mRNA contributes to protection against
H. pylori
infection by downregulating LOX-1 and thus reducing
H. pylori
adhesion.
The intestinal epithelium compartmentalizes the sterile bloodstream and the commensal bacteria in the gut. Accumulating evidence suggests that this barrier is impaired in sepsis, aggravating systemic ...inflammation. Previous studies reported that cathelicidin is differentially expressed in various tissues in sepsis. However, its role in sepsis-induced intestinal barrier dysfunction has not been investigated.
To examine the role of cathelicidin in polymicrobial sepsis, cathelicidin wild-(Cnlp
) and knockout (Cnlp
) mice underwent cecal-ligation and puncture (CLP) followed by the assessment of septic mortality and morbidity as well as histological, biochemical, immunological, and transcriptomic analyses in the ileal tissues. We also evaluated the prophylactic and therapeutic efficacies of vitamin D3 (an inducer of endogenous cathelicidin) in the CLP-induced murine polymicrobial sepsis model.
The ileal expression of cathelicidin was increased by three-fold after CLP, peaking at 4 h. Knockout of Cnlp significantly increased 7-day mortality and was associated with a higher murine sepsis score. Alcian-blue staining revealed a reduced number of mucin-positive goblet cells, accompanied by reduced mucin expression. Increased number of apoptotic cells and cleavage of caspase-3 were observed. Cnlp deletion increased intestinal permeability to 4kD fluorescein-labeled dextran and reduced the expression of tight junction proteins claudin-1 and occludin. Notably, circulating bacterial DNA load increased more than two-fold. Transcriptome analysis revealed upregulation of cytokine/inflammatory pathway. Depletion of Cnlp induced more M1 macrophages and neutrophils compared with the wild-type mice after CLP. Mice pre-treated with cholecalciferol (an inactive form of vitamin D3) or treated with 1alpha, 25-dihydroxyvitamin D3 (an active form of VD3) had decreased 7-day mortality and significantly less severe symptoms. Intriguingly, the administration of cholecalciferol after CLP led to worsened 7-day mortality and the associated symptoms.
Endogenous cathelicidin promotes intestinal barrier integrity accompanied by modulating the infiltration of neutrophils and macrophages in polymicrobial sepsis. Our data suggested that 1alpha, 25-dihydroxyvitamin D3 but not cholecalciferol is a potential therapeutic agent for treating sepsis.
This quantitative systematic review compared the efficacy and safety of ephedrine with phenylephrine for the prevention and treatment of hypotension during spinal anesthesia for cesarean delivery. ...Seven randomized controlled trials (n = 292) were identified after a systematic search of electronic databases (MEDLINE, EMBASE, The Cochrane Controlled Trials Registry), published articles, and contact with authors. Outcomes assessed were maternal hypotension, hypertension and bradycardia, and neonatal umbilical cord blood pH values and Apgar scores. For the management (prevention and treatment) of maternal hypotension, there was no difference between phenylephrine and ephedrine (relative risk RR of 1.00; 95% confidence interval CI, 0.96-1.06). Maternal bradycardia was more likely to occur with phenylephrine than with ephedrine (RR of 4.79; 95% CI, 1.47-15.60). Women given phenylephrine had neonates with higher umbilical arterial pH values than those given ephedrine (weighted mean difference of 0.03; 95% CI, 0.02-0.04). There was no difference between the two vasopressors in the incidence of true fetal acidosis (umbilical arterial pH value of <7.2; RR of 0.78; 95% CI, 0.16-3.92) or Apgar score of <7 at 1 and 5 min. This systematic review does not support the traditional idea that ephedrine is the preferred choice for the management of maternal hypotension during spinal anesthesia for elective cesarean delivery in healthy, nonlaboring women.
Phenylephrine and ephedrine to manage hypotension during spinal anesthesia for elective cesarean delivery were compared in this systematic review. Women given ephedrine had neonates with lower umbilical cord blood pH values compared with those given phenylephrine. However, no differences in the incidence of fetal acidosis (pH value of <7.2) or neonatal Apgar scores were found.
Signal transducer and activator of transcription 3 (Stat3) is known to induce cell proliferation and inflammation by regulating gene transcription. Recent studies showed that Stat3 modulates ...nociceptive transmission by reducing spinal astrocyte proliferation. However, it is unclear whether Stat3 also contributes to the modulation of nociceptive transmission by regulating inflammatory response in spinal astrocytes. This study aimed at investigating the role of Stat3 on neuroinflammation during development of pain in rats after intrathecal injection of lipopolysaccharide (LPS).
Stat3 specific siRNA oligo and synthetic selective inhibitor (Stattic) were applied to block the activity of Stat3 in primary astrocytes or rat spinal cord, respectively. LPS was used to induce the expression of proinflammatory genes in all studies. Immunofluorescence staining of cells and slices of spinal cord was performed to monitor Stat3 activation. The impact of Stat3 inhibition on proinflammatory genes expression was determined by cytokine antibody array, enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Mechanical allodynia, as determined by the threshold pressure that could induce hind paw withdrawal after application of standardized von Frey filaments, was used to detect the effects of Stat3 inhibition after pain development with intrathecal LPS injection.
Intrathecal injection of LPS activated Stat3 in reactive spinal astrocytes. Blockade of Stat3 activity attenuated mechanical allodynia significantly and was correlated with a lower number of reactive astrocytes in the spinal dorsal horn. In vitro study demonstrated that Stat3 modulated inflammatory response in primary astrocytes by transcriptional regulation of chemokine expression including Cx3cl1, Cxcl5, Cxcl10 and Ccl20. Similarly, inhibition of Stat3 reversed the expression of these chemokines in the spinal dorsal horn.
Stat3 acted as a transcriptional regulator of reactive astrocytes by modulating chemokine expression. Stat3 regulated inflammatory response in astrocytes and contributed to pain modulation. Blockade of Stat3 represents a new target for pain control.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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