Early infection during burn-induced inflammatory response results in increased mortality and p38-mediated neutrophil dysfunction

2010 ◽  
Vol 299 (3) ◽  
pp. R918-R925 ◽  
Author(s):  
Samuel G. Adediran ◽  
Derrick J. Dauplaise ◽  
Kevin R. Kasten ◽  
Johannes Tschöp ◽  
Jonathan Dattilo ◽  
...  

Following burn injury, the host is susceptible to bacterial infections normally cleared by healthy patients. We hypothesized that during the systemic immune response that follows scald injury, the host's altered immune status increases infection susceptibility. Using a murine model of scald injury under inhaled anesthesia followed by intraperitoneal infection, we observed increased neutrophil numbers and function at postburn day (PBD) 1 compared with sham-burned and PBD4 mice. Further, increased mortality, bacteremia, and serum IL-6 were observed in PBD1 mice after Pseudomonas aeruginosa (PA) infection compared with sham-burned and PBD4 mice infected with PA. To examine these disparate responses, we investigated neutrophils isolated at 5 and 24 h following PA infection from PBD1 and sham-burned mice. Five hours after infection, there was no significant difference in number of recruited neutrophils; however, neutrophils from injured mice had decreased activation, active-p38, and oxidative burst compared with sham-burned mice. In direct contrast, 24 h after infection, we observed increased numbers, active-p38, and oxidative burst of neutrophils from PBD1 mice. Finally, we demonstrated that in neutrophils isolated from PBD1 mice, the observed increase in oxidative burst was p38 dependent. Altogether, neutrophil activation and function from thermally injured mice are initially delayed and later exacerbated by a p38-dependent mechanism. This mechanism is likely key to the observed increase in bacterial load and mortality of PBD1 mice infected with PA.

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S88-S89
Author(s):  
Breanne H Gibson ◽  
Matthew T Duvernay ◽  
Stephen Gondek ◽  
Jonathan G Schoenecker

Abstract Introduction Platelet dysfunction has been demonstrated as a part of burn induced coagulopathy (BIC), however, the etiology and clinical significance are unknown. Determining the etiology and clinical significance of BIC platelet dysfunction is difficult in humans due to heterogeneity of injuries and treatment. The goal of this study was to develop a murine model of BIC burn-induced platelet dysfunction to allow for high-throughput investigation of the mechanisms and the possible effects platelet dysfunction has on burn outcomes. Methods Using an established murine model of burn injury, we investigated plasma and cellular markers of BIC. Under adequate anesthesia and analgesia six-week-old C57BL6/J mice were administered a ~30% TBSA dorsal burn by scalding. Sham animals received identical preparation and resuscitation without the burn injury. Blood was collected at 6-, 24-, and 48-hours post-burn for measurement of platelet function, and plasma was isolated for protein measurements of coagulopathy (N=5 per group per time point). Results Like findings in humans, mice exhibited systemic markers of BIC (excess coagulation, fibrinolysis, and inflammation) within the first 6–24 hours post-burn. Platelets in whole blood were treated with platelet agonists ADP and PAR4-activating peptide (PAR4AP), and markers of platelet signaling and function (P-selectin expression and GpIIb/IIIa activation) were measured by flow cytometry. At 6 hours post-procedure, platelets from burn mice exhibited a slight, insignificant increase in markers of activation and response to stimulation compared with platelets from sham mice. At 24 hours post-burn, burn mice exhibited a significant decrease in platelet count (P< 0.02) and platelet function indicated by reduced GpIIb/IIIa activation (P< 0.01) and P-selectin expression (P< 0.05)in response to ADP and PAR4-AP compared with sham mice. Platelet function began to return at 48 hours post-burn with no significant difference between groups. Conclusions Platelet loss and dysfunction occur after burn injury, but the consequence of these effects is not well understood. The findings in this study are consistent across multiple experiments and resembled platelet dysfunction observed in different human traumatic injuries, validating the murine model as an inexpensive and efficient model of human injury in which to study platelet defects and the molecular mechanisms driving them.


Author(s):  
Valentin Sencio ◽  
Marina Gomes Machado ◽  
François Trottein

AbstractBacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host’s defense against viral respiratory infections. The gut microbiota’s composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota’s composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung–gut axis in coronavirus disease 2019.


Author(s):  
Chimdimma Noelyn Onah ◽  
Richard Allmendinger ◽  
Julia Handl ◽  
Ken W. Dunn

With a reduction in the mortality rate of burn patients, length of stay (LOS) has been increasingly adopted as an outcome measure. Some studies have attempted to identify factors that explain a burn patient’s LOS. However, few have investigated the association between LOS and a patient’s mental and socioeconomic status. There is anecdotal evidence for links between these factors; uncovering these will aid in better addressing the specific physical and emotional needs of burn patients and facilitate the planning of scarce hospital resources. Here, we employ machine learning (clustering) and statistical models (regression) to investigate whether segmentation by socioeconomic/mental status can improve the performance and interpretability of an upstream predictive model, relative to a unitary model. Although we found no significant difference in the unitary model’s performance and the segment-specific models, the interpretation of the segment-specific models reveals a reduced impact of burn severity in LOS prediction with increasing adverse socioeconomic and mental status. Furthermore, the socioeconomic segments’ models highlight an increased influence of living circumstances and source of injury on LOS. These findings suggest that in addition to ensuring that patients’ physical needs are met, management of their mental status is crucial for delivering an effective care plan.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Surette ◽  
A Narang ◽  
R Bae ◽  
H Hong ◽  
Y Thomas ◽  
...  

Abstract Background A novel, recently FDA-authorized software uses deep learning (DL) to provide prescriptive transthoracic echocardiography (TTE) guidance, allowing novices to acquire standard TTE views. The DL model was trained by >5,000,000 observations of the impact of probe motion on image orientation/quality. This study evaluated whether novice-acquired TTE images guided by this software were of diagnostic quality in patients with and without implanted electrophysiological (EP) devices, focusing on RV size and function, which were thought to be sensitive to EP devices. Some aspects of the study have previously been presented. Methods 240 patients (61±16 years old, 58% male, 33% BMI >30 kg/m2, 91% with cardiac pathology) were recruited. 8 nurses without echo experience each acquired 10 view TTEs in 30 patients guided by the software. 235 of the patients were also scanned by a trained sonographer without assistance from the software. 5 Level 3 echocardiographers independently assessed the diagnostic quality of the TTEs acquired by the nurses and sonographers to evaluate the effect of EP devices on DL software performance. Results Nurses using the AI-guided acquisition software acquired TTEs of sufficient quality to make qualitative assessments of right ventricular (RV) size and function in greater than 80% of cases for patients with and without implanted EP devices (Table). There was no significant difference between nurse- and sonographer-acquired scans. Conclusion These results indicate that new DL software can guide novices to obtain TTEs that enable qualitative assessment of RV size even in the presence of implanted EP devices. The results of the comparison to sonographer-acquired exams indicate the software performance is robust to presence of pacemaker/ICD leads visible in the images (Figure). Nurse-acquired TTE with visible ICD lead Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Caption Health, Inc.


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 428
Author(s):  
Pavel Kvapil ◽  
Joško Račnik ◽  
Marjan Kastelic ◽  
Jiřina Marková ◽  
Jean-Benjamin Murat ◽  
...  

Monitoring of infectious diseases is one of the most important pillars of preventive medicine in zoos. Screening for parasitic and bacterial infections is important to keep animals and equipment safe from pathogens that may pose a risk to animal and human health. Zoos usually contain many different animal species living in proximity with people and wild animals. As an epidemiological probe, 188 animals (122 mammals, 65 birds, and one reptile) from a zoo in Slovenia were examined for selected pathogens. Antibodies to Toxoplasma gondii and Neospora caninum were detected by ELISA in 38% (46/122) and 3% (4/122) of mammals, and in 0% (0/64) and 2% (1/57) of birds, respectively; the reptile (0/1) was negative. A statistically significant difference in T. gondii prevalence was found in Carnivora compared to Cetartiodactyla and primate antibodies to Encephalitozoon cuniculi were detected by IFAT in 44% (52/118) of mammals and 20% (11/56) of birds, respectively; the reptile (0/1) was negative. Herbivores had a higher chance of being infected with E. cuniculi compared to omnivores. Antibodies to Chlamydia abortus and Coxiella burnetii were not detected in any of the 74 tested zoo animals. The sera of 39 wild rodents found in the zoo were also examined; they were negative for all three parasites. The parasite T. gondii was detected by PCR in the tissue of two mute swans (Cygnus olor), three eastern house mice (Mus musculus), one yellow-necked field mouse (Apodemus flavicollis), and one striped field mouse (A. agrarius). Positive samples were genotyped by a single multiplex PCR assay using 15 microsatellite markers; one sample from a mute swan was characterized as type II. This micro-epidemiological study offers a better understanding of pathogens in zoo animals and an understanding of the role of zoos in biosurveillance.


2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S162-S163
Author(s):  
Jennifer B Radics-Johnson ◽  
Daniel W Chacon ◽  
Li Zhang

Abstract Introduction Burn camps provide a unique environment and activities for children that have experienced a burn-injury. Positive outcomes from attending burn camp include increased self-esteem, decreased feelings of isolation and a greater sense of self-confidence. In a 3-year retrospective review of camper evaluations from one of the largest and longest running week-long burn camps in the nation for ages 5–17, we aimed to assess if a child’s gender, age, TBSA or ethnicity affected the impact that burn camp had on a child. Methods A 3-year retrospective review of a Burn Camp’s camper evaluation forms was conducted for campers that attended burn camp between 2017–2019. Camp rosters were reviewed to determine the camper gender, age, TBSA and ethnicity. Camper self-evaluation forms completed at the end of each camp session were reviewed to record camper responses to questions regarding their opinions on the impact camp had on them as well as how camp will impact their lives once they return home. Categorical variables were summarized as frequency and percentage, and continuous variables were described as median and range. To check the relationship between two categorical variables, Chi-square test was used. To compare the continuous variable among groups, Kruskal-Wallis ANOVA was used. Statistical significance was declared based on a p value< 0.5. Results Within 2017–2019, there were 413 camper records. Participants’ demographic characteristics are summarized in Table 1. There were 208 males (50.3%) and 205 females (49.6%). The median age of campers were 11.86, 12.44 and 12.45 for 2017–2019, with the range from 5.16 years to 17.96 years. The median TBSA were 20, 20 and 18 for 2017–2019, with the range from 0.08 to 90. Collectively there were 47.7% Hispanic (n= 197); 24.2% Whites (n=100); 13.1% Black (n= 54); 4.6% Asian (n=19) and 7.7% Other (n=32). There were 395 camper self-evaluation forms submitted. Results of three questions there we were interested in are summarized collectively in Table 2. 57% of campers responded, “Yes, Definitely” to the question “After going to this event, will you feel more comfortable being around your classmates or friends?” 54% responded, “ Yes, Definitely” to the question “Do you feel more confidents in sharing your burn story with others when returning home?” and 51% responded “Yes, Definitely” to “Did you learn anything that will help you when you return home?” Conclusions In analyzing the camper responses, there was no statistically significant difference in responses comparing gender, age, TBSA or ethnicity.


2019 ◽  
Vol 29 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Zahra Hoodbhoy ◽  
Nuruddin Mohammed ◽  
Nadeem Aslam ◽  
Urooj Fatima ◽  
Salima Ashiqali ◽  
...  

AbstractObjective:The objective of this study was to assess differences in myocardial systolic and diastolic function and vascular function in children 2−5 years of age born to diabetic as compared to non-diabetic mothers.Methods:This study was a retrospective cohort conducted in 2016 at The Aga Khan University Hospital, Karachi, Pakistan. It included children between 2 and 5 years of age born to mothers with and without exposure to diabetes in utero (n = 68 in each group) and who were appropriate for gestational age. Myocardial morphology and function using echocardiogram and carotid intima media thickness (cIMT) and pulse wave velocity was performed to evaluate cardiac function as well as macrovascular remodelling in these children. Multiple linear regression was used to compare the groups.Results:There was no significant difference in cardiac morphology, myocardial systolic and diastolic function, and macrovascular assessment between the exposed and unexposed groups of AGA children. Subgroup analysis demonstrated a significantly decreased mitral E/A ratio in children whose mothers were on medications as compared to those on dietary control (median [IQR] = 1.7 [1.6–1.9] and 1.56 [1.4–1.7], respectively, p = 0.02), and a higher cIMT in children whose mothers were on medication as compared to controls (0.48 [0.44–0.52] and 0.46 [0.44–0.50], respectively, p = 0.03).Conclusion:In utero exposure to uncontrolled maternal diabetes has an effect on the cardiovascular structure and function in children aged 2−5 years. However, future work requires long-term follow-up from fetal to adult life to assess these changes over the life course.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Scott Allan Orr

AbstractCarillons are a diverse and global form of musical and civic heritage: musical instruments comprised of a series of 23 or more bells, typically hung in a tower-like structure, tuned chromatically and played from a touch-sensitive manual and pedal console using an elaborate mechanical action. Carillon bells have a distinct series of musical overtones which should be accurately tuned to one another and with other bells they sound alongside. Although these overtones have been previously studied ex situ, this study assesses the acoustic characteristics of two early-twentieth century carillons in Toronto, Canada as a combination of structure, bells, and mechanical action. Thus, the instrument and its context are considered holistically, more accurately reflecting the musical sensitivity of a carillonist. Spectral analysis of audio samples of each bell at different musical dynamic levels enabled the analysis of the acoustic qualities of the bells and the mechanical action of the instruments. The tuning of bells in the instruments varied; most importantly, there was a significant difference between the audial intensity of the bell tones produced by the instruments, demonstrating the importance of the mechanical action as part of the ‘carillon system’. This was represented with a resistive power-law model, that represents the sensitivity of intensity to carillonist musical dynamic level. A discussion of the implications for artistic and heritage practice follows. Understanding the in situ physical acoustics of the carillon as a holistic instrument in its context informs performers, arrangers, and composers of how they can best embrace the instrument’s unique qualities to improve artistic pursuits and support the appreciation of carillons as heritage instruments and function as civic voices.


2018 ◽  
Vol 14 (4) ◽  
pp. 223-230 ◽  
Author(s):  
M. Andrews-Rudd ◽  
C. Farmer-Day ◽  
H.M. Clayton ◽  
J.M. Williams ◽  
D.J. Marlin

Although stirrups may be considered an essential part of equestrian equipment, there is little research describing their use and function. The aim of the present study was to compare stirrup lengths chosen for flatwork by novice and experienced riders, and to measure the associated leg position and knee angles. Ten novice and ten experienced riders, with kinematic markers attached to their greater trochanter, lateral femoral epicondyle, and lateral fibular malleolus, mounted three horses and a mechanical horse. The riders selected an appropriate stirrup length for flatwork by adjusting the unnumbered stirrup leathers. Stirrup length was measured and expressed as a percentage of the rider’s leg length measured from the greater trochanter to the floor when standing. Lateral photographs were taken from both sides with the riders mounted on each horse in a standing position. The kinematic markers were digitised to measure knee angle and ankle position relative to the hip in the anteroposterior direction. Within riders, there was no significant difference in stirrup length between the three live horses or between the mechanical horse and live horse. Experienced riders consistently selected a significantly longer stirrup length as a percentage of their leg length compared with novice riders (combined data for live horses and mechanical horse; P=0.005). Experienced riders demonstrated a significantly larger knee angle (combined data for live horses and mechanical horse) compared with novice riders (118±8° and 109±7°, respectively; P=0.016). Novice riders had a significantly larger knee angle on the mechanical horse compared with the live horse (115±9° versus 107±9°, respectively; P=0.003). The relatively longer stirrup length selected by experienced riders is thought to reflect the development of an independent seat, which implies the ability to move the legs independently of the pelvis. The chair seat adopted by novice riders on the mechanical horse could be considered counter to improving their equitation skills.


1997 ◽  
Vol 273 (4) ◽  
pp. H1824-H1831 ◽  
Author(s):  
Masakazu Obayashi ◽  
Masafumi Yano ◽  
Michihiro Kohno ◽  
Shigeki Kobayashi ◽  
Taketo Tanigawa ◽  
...  

The goal of this study was to examine the effect of an angiotensin II type 1 (AT1)-receptor antagonist (TCV-116) on left ventricular (LV) geometry and function during the development of pressure-overload LV hypertrophy. A low (LD; 0.3 mg ⋅ kg−1 ⋅ day−1) or a high (HD; 3.0 mg ⋅ kg−1 ⋅ day−1) dose of TCV-116 was administered to abdominal aortic-banded rats over 4 wk, and hemodynamics and morphology were then evaluated. In both LD and HD groups, peak LV pressures were decreased to a similar extent compared with the vehicle-treated group but stayed at higher levels than in the sham-operated group. In the LD group, both end-diastolic wall thickness (3.08 ± 0.14 mm) and myocyte width (13.3 ± 0.1 μm) decreased compared with those in the vehicle-treated group (3.67 ± 0.19 mm and 15.3 ± 0.1 μm, respectively; both P < 0.05). In the HD group, myocyte length was further decreased (HD: 82.6 ± 2.6, LD: 94.1 ± 2.9 μm; P < 0.05) in association with a reduction in LV midwall radius (HD: 3.36 ± 0.12, LD: 3.60 ± 0.14 mm; P < 0.05) and peak midwall fiber stress (HD: 69 ± 8, LD: 83 ± 10 × 103dyn/cm2; P < 0.05). There was no significant difference in cardiac output among all groups. The AT1-receptor antagonist TCV-116 induced an inhibition of the development of pressure-overload hypertrophy. Morphologically, not only the width but also the length of myocytes was attenuated with TCV-116, leading to a reduction of midwall radius and hence wall stress, which in turn may contribute to a preservation of cardiac output.


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