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Many children care about animals yet are accepting of meat consumption. This may reflect a disconnect between children's meat eating, food-systems knowledge, and their moral evaluations. A theoretical framework is proposed for understanding the developmental trajectory of this disconnection. We discuss its components and the implications for dietary interventions. [ABSTRACT FROM AUTHOR]

This paper argues that Leibniz's use of the concept of "automaton" to characterize the nature of souls and bodies of living beings constitutes a systematic critique of Descartes' earlier use of automata. Whereas Descartes conceived non-human animals in terms of mechanical automata, he also denied that the human rational soul can be modeled on the nature of an automaton. In contrast, Leibniz understood living things to involve both an organic body, or "natural automaton," as well as an immaterial soul, or "spiritual automaton," that spontaneously produces its own perceptions. In extending the concept of the automaton to souls, Leibniz rejected key Cartesian assumptions about animals and free will and draws on the concept of the automaton to understand a range of cognitive capacities including volition. Leibniz thus occupies a distinctive place in the history of the use of automata to understand the nature of living things. [ABSTRACT FROM AUTHOR]

Evidence is mounting that non-genetic inheritance impacts evolution, however, how conserved the underlying processes are remains unexplored. Klughammer et al. investigated DNA methylation across the animal kingdom, one important mechanism of non-genetic inheritance. Using a dataset encompassing 580 species, the authors identified conserved associations between sequence and DNA methylation. [ABSTRACT FROM AUTHOR]

This article examines the ethical principles underlying the Declaration of Helsinki as an internationally agreed justificatory framework for human medical research. The aim of the analysis is to consider the potential usefulness of these principles for defining an internationally agreed ethical 'best practice' in clinical veterinary research (CVR). It is suggested that the specific ethical responsibilities of the clinician to protect the interests of their patient when conducting medical research may be translated into the veterinary setting. Through exploring risk and harm, unproven interventions, vulnerability and informed consent, the article identifies the ethical risks of CVR. It is shown that veterinary regulators in the UK and the European Union have addressed these concerns to varying degrees; however, disagreements over the appropriateness of specific CVR practices are identified. A commitment to collaborative exploration of the benefits and challenges of implementing a Declaration of Helsinki for Animals is proposed. [ABSTRACT FROM AUTHOR]

Hexavalent chromium (CrVI)-exposure of suckling rats has been shown to delay tooth eruption. However, the effects of CrVI-exposure on bone formation at the base of the alveolus, which provides a motive force for tooth eruption in the early stages of the process, remain unknown. The present work sought to evaluate the effect of CrVI-exposure on bone formation at the base of the alveolus during the intraosseous stage of tooth eruption in suckling rats, using histomorphometric and immunohistochemical studies. Experimental animals received 12.5 mg/kg-bw/day of potassium dichromate dissolved in saline solution by gavage starting on day 4 of the experiment; controls similarly received an equivalent volume of saline. All the animals were euthanized at the age of 9 days. The base of the developing alveolus at the level of the mesial root of the first lower molar was analyzed histomorphometrically and immunohistochemically. Data were statistically analyzed using student's t- test, with statistical significance set at p < 0.05. CrVI-exposed animals showed lower bone volume and height at the base of the alveolus, a significant preponderance of bone rest on the surface adjacent to the dental follicle, and a significantly lower percentage of positive Runt-related transcription factor-2 (RUNX2+) osteoblasts and a significantly higher number of mesenchymal-like RUNX2+ cells at the latter site. CrVI-exposure during lactation affects bone formation at the base of the developing alveolus, delaying tooth eruption. These findings underscore the importance of controlling drinking water levels of toxic substances since their effects can alter the growth and development of individuals exposed during early childhood. [ABSTRACT FROM AUTHOR]

Recombinant human collagen peptide (RCP) is a recombinantly created xeno-free biomaterial enriched in arginine-glycine-aspartic acid sequences with good processability whose use for regenerative medicine applications is under investigation. The biocompatibility and osteogenic ability of RCP granules combined with β-tricalcium phosphate (TCP) submicron particles (β-TCP/RCP) were recently demonstrated. In the present study, β-TCP/RCP was implanted into experimental periodontal tissue defects created in beagles to investigate its regenerative effects. An RCP solution was lyophilized, granulated, and thermally cross-linked into particles approximately 1 mm in diameter. β-TCP dispersion (1 wt%; 500 μL) was added to 100 mg of RCP granules to form β-TCP/RCP. A three-walled intrabony defect (5 mm × 3 mm × 4 mm) was created on the mesial side of the mandibular first molar and filled with β-TCP/RCP. A micro-computed tomography image analysis performed at 8 weeks postoperative showed a significantly greater amount of new bone after β-TCP/RCP grafting (2.2-fold, P < 0.05) than after no grafting. Histological findings showed that the transplanted β-TCP/RCP induced active bone-like tissue formation including tartaric acid-resistant acid phosphatase– and OCN-positive cells as well as bioabsorbability. Ankylosis did not occur, and periostin-positive periodontal ligament-like tissue formation was observed. Histological measurements performed at 8 weeks postoperative revealed that β-TCP/RCP implantation formed 1.7-fold more bone-like tissue and 2.1-fold more periodontal ligament-like tissue than the control condition and significantly suppressed gingival recession and epithelial downgrowth (P < 0.05). β-TCP/RCP implantation promoted bone-like and periodontal ligament–like tissue formation, suggesting its efficacy as a periodontal tissue regenerative material. [ABSTRACT FROM AUTHOR]

Background: Exposure to early life adversities (ELA) can influence a plethora of biological mechanisms leading to stress-related disorders later in life through epigenetic mechanisms, such as microRNAs (miRs). MiR-34 is a critical modulator of stress response and stress-induced pathologies and a link between ELA and miR-34a has been reported.Methods: Here using our well-established model of ELA (Repeated Cross Fostering) we investigate the behavioral long-term effects of ELA in male and female mice. We also assess basal and ELA-induced miR-34a expression in adult mice and investigate whether ELA affects the later miR-34a response to adult acute stress exposure across brain areas (medial preFrontal Cortex, Dorsal Raphe Nuclei) and peripheral organs (heart, plasma) in animals from both sexes. Finally, based on our previous data demonstrating the critical role of Dorsal Raphe Nuclei miR-34a expression in serotonin (5-HT) transmission, we also investigated prefrontal-accumbal 5-HT outflow induced by acute stress exposure in ELA and Control females by in vivo intracerebral microdialysis.Results: ELA not just induces a depressive-like state as well as enduring changes in miR-34a expression, but also alters miR-34a expression in response to adult acute stress exclusively in females. Finally, altered DRN miR-34a expression is associated with prefrontal-accumbal 5-HT release under acute stress exposure in females.Limitations: Translational study on humans is necessary to verify the results obtained in our animal models of ELA-induced depression.Conclusions: This is the first evidence showing long-lasting sex related effects of ELA on brain and peripheral miR-34a expression levels in an animal model of depression-like phenotype. [ABSTRACT FROM AUTHOR]

Ultrafast ultrasound is an emerging imaging modality derived from standard medical ultrasound. It allows for a high spatial resolution of 100 μm and a temporal resolution in the millisecond range with techniques such as ultrafast Doppler imaging. Ultrafast Doppler imaging has become a priceless tool for neuroscience, especially for visualizing functional vascular structures and navigating the brain in real time. Yet, the quality of a Doppler image strongly depends on experimental conditions and is easily subject to artifacts and deterioration, especially with transcranial imaging, which often comes at the cost of higher noise and lower sensitivity to small blood vessels. A common solution to better visualize brain vasculature is either accumulating more information, integrating the image over several seconds or using standard filter-based enhancement techniques, which often over-smooth the image, thus failing both to preserve sharp details and to improve our perception of the vasculature. In this study we propose combining the standard Doppler accumulation process with a real-time enhancement strategy, based on deep-learning techniques, using perceptual loss (PerceptFlow). With our perceptual approach, we bypass the need for long integration times to enhance Doppler images. We applied and evaluated our proposed method on transcranial Doppler images of mouse brains, outperforming state-of-the-art filters. We found that, in comparison to standard filters such as the Gaussian filter (GF) and block-matching and 3-D filtering (BM3D), PerceptFlow was capable of reducing background noise with a significant increase in contrast and contrast-to-noise ratio, as well as better preserving details without compromising spatial resolution. [ABSTRACT FROM AUTHOR]

Amplitude modulation (AM) suppresses tissue signals and detects microbubble signals in contrast-enhanced ultrasound (CEUS) and is often implemented with checkerboard apertures. However, possible crosstalk between transmitting and non-transmitting array elements may compromise tissue suppression in AM. Using AM aperture patterns other than the conventional checkerboard approach (one on, one off) may reduce the degree of crosstalk and increase the contrast-to-tissue-ratio (CTR) compared with conventional AM. Furthermore, previous studies have reported that the phase difference between the echoes in AM pulsing sequences may be used to segment tissue and microbubbles and improve tissue signal suppression and the CTR of CEUS images. However, the CTR of the image produced by alternative AM aperture patterns and the effect of segmentation approach on these alternative apertures have not been investigated. We evaluated a number of AM aperture patterns to find an optimal AM aperture pattern that provides the highest CTR. We found that the aperture that uses alternating groups of two elements, AM2, had the highest CTR for the probe evaluated. In addition, a segmentation technique based on echo phase differences (between the full and half-pulses, ΔΦAM, between the complementary half-pulses, ΔΦhalf, and the maximum of the two ΔΦmax) was also considered in the AM aperture optimization process. The segmentation approach increases the CTR by about 25 dB for all apertures. Finally, AM2 segmented with ΔΦmax had a 7-dB higher CTR in a flow phantom and a 6-dB higher contrast in a perfused pig liver than conventional AM segmented with ΔΦAM, and it is the optimal transmit aperture design. [ABSTRACT FROM AUTHOR]

Adaptive Bayesian regularized cardiac strain imaging (ABR-CSI) uses raw radiofrequency signals to estimate myocardial wall contractility as a surrogate measure of relative tissue elasticity incorporating regularization in the Bayesian sense. We determined the feasibility of using ABR-CSI -derived strain for in vivo longitudinal monitoring of cardiac remodeling in a murine ischemic injury model (myocardial infarction [MI] and ischemia-reperfusion [IR]) and validated the findings against ground truth histology. We randomly stratified 30 BALB/CJ mice (17 females, 13 males, median age = 10 wk) into three surgical groups (MI = 10, IR = 12, sham = 8) and imaged pre-surgery (baseline) and 1, 2, 7 and 14 d post-surgery using a pre-clinical high-frequency ultrasound system (VisualSonics Vevo 2100). We then used ABR-CSI to estimate end-systolic and peak radial (er) and longitudinal (el) strain estimates. ABR-CSI was found to have the ability to serially monitor non-uniform cardiac remodeling associated with murine MI and IR non-invasively through temporal variation of strain estimates post-surgery. Furthermore, radial end-systole (ES) strain images and segmental strain curves exhibited improved discrimination among infarct, border and remote regions around the myocardium compared with longitudinal strain results. For example, the MI group had significantly lower (Friedman's with Bonferroni-Dunn test, p = 0.002) ES er values in the anterior middle (infarcted) region at day 14 (n = 9, 9.23 ± 7.39%) compared with the BL group (n = 9, 44.32 ± 5.49). In contrast, anterior basal (remote region) mean ES er values did not differ significantly (non-significant Friedman's test, χ2 = 8.93, p = 0.06) at day 14 (n = 6, 33.05 ± 6.99%) compared with baseline (n = 6, 34.02 ± 6.75%). Histology slides stained with Masson's trichrome (MT) together with a machine learning model (random forest classifier) were used to derive the ground truth cardiac fibrosis parameter termed histology percentage of myocardial fibrosis (PMF). Both radial and longitudinal strain were found to have strong statistically significant correlations with the PMF parameter. However, radial strain had a higher Spearman's correlation value (εresρ = -0.67, n = 172, p < 0.001) compared with longitudinal strain (εlesρ = -0.60, n = 172, p < 0.001). Overall, the results of this study indicate that ABR-CSI can reliably perform non-invasive detection of infarcted and remote myocardium in small animal studies. [ABSTRACT FROM AUTHOR]

Background: Although the Wistar Kyoto (WKY) rat has been consistently recognized as an animal model with endogenous depression, the exact molecular mechanisms underlying its genetic susceptibility to depression remain undetermined.Methods: Compared with the Wistar rats, the depression-like behaviors of the male WKY ones were evaluated by both the sucrose preference test and forced swimming test. Golgi staining analysis was conducted to access the dendritic morphology. TMT-labelled quantitative proteomics analyses were respectively performed in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and hippocampus (Hip), followed by KEGG enrichment-based clustering analysis, Venn diagram analysis, and Pearson correlation analysis.Results: The WKY strain showed significant differences in both the depression-like behaviors and synaptic plasticity. Moreover, the WKY model displayed markedly distinct differentially-expressed protein (DEP) profiles, with minor differences between the WKY subgroups. A cerebral regional commonality and specificity were evident in the signaling pathways enriched in the WKY model, and a total of 15 brain region-specific DEPs were identified to closely correlate with the depression-like phenotypes (in the mPFC: Lrrc8d, Dcun1d2, and Mtnd5; in the NAc: Ccdc154, Sec14l2, Kif2a, LOC680322, Me1, Mknk1, and Ret7; in the Hip: Sec14l2, Serpinf2, LOC103694855, Fam13c, and Loxl1). Data were available via ProteomeXchange with identifier PXD029079.Limitations: Female WKY rats are not included, and the roles of these candidate DEPs in depression remain further elucidation.Conclusion: The present study further evidences the brain region-specific protein signatures in the male WKY model with endogenous depression, providing novel insights into the pathogenesis of depression in males. [ABSTRACT FROM AUTHOR]

Background: Our recent study demonstrated that selective aryl hydrocarbon receptor modulators (SAhRMs), such as 1,4-dihydroxy-2-napthoic acid (DHNA) act as antidepressants in female mice. Given that some effects of certain SAhRMs are known to also be mediated via estrogen receptor signaling, this study examined whether the effects of SAhRMs on mood, emotional state, and cognition are sex-dependent.Methods: C57BL/6N mice were fed with vehicle or 20 mg/kg DHNA for three weeks prior to four weeks of unpredictable chronic mild stress (UCMS). Mice were examined for depression-like behaviors (sucrose preference, forced swim test (FST), splash test, tape groom test), emotional state (open-field test, light/dark test, marble burying, novelty-induced hypophagia, elevated-plus maze), and cognition (object location recognition, novel object recognition, Morris water maze).Results: In females, UCMS decreased sucrose preference and increased FST immobility time; both effects were prevented by DHNA. In males, UCMS increased FST immobility time, and increased the latency to groom in the splash test. These effects were not mitigated by DHNA. However, in males, UCMS induced an increase in novelty-induced locomotion, an increase in the time spent in the light compartment in the L/D test, and an increase in the time spent with an object in a novel location. These effects were prevented by DHNA.Conclusions: Our findings indicate that DHNA has high potential to act as antidepressants in females. However, given classical interpretation, DHNA did not appear to act as an antidepressant in males. Nonetheless, our findings indicate that DHNA can mitigate stress effects and reactivity in males. [ABSTRACT FROM AUTHOR]

Background: Possible relationships between suicidal ideation and biopsychosocial predictors in older age are unclear. In the population-based Salus in Apulia Study, we investigated the relationships among biomarkers, socio-demographic, psychopathological, inflammatory and metabolic characteristics and suicidal ideation in 1252 older subjects.Methods: Suicidal ideation was evaluated with the brief version of the Columbia-Suicide Severity Rating Scale. Apolipoprotein E (APOE) genotype and inflammatory profile [interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP)] were evaluated. A machine learning algorithm, the Random Forest (RF), selected potential biopsychosocial factors associated to suicidal ideation.Results: Suicidal ideators accounted for 2.32 % of subjects, were female, smokers, and obese with multimorbidity. After adjusting for age, gender, education and social dysfunction, logistic regression analyses revealed that suicidal ideation was associated to late-life depression (LLD) (odds ratio:21.71,95 % confidence interval:9.22-51.14). In the full RF model, asthma was the most important contributor to suicidal ideation. In the final RF model, education, age, and mild cognitive impairment followed by gender and global cognition were considered the most important contributors. Among biomarkers, in the final RF model, IL-6 followed by TNF-α, APOE ε4 allele presence, CRP and high-density lipoprotein cholesterol contributed most to suicidal ideation.Limitations: A relatively small number of older subjects with suicidal ideation (2.3 %); we did not distinguish between active and passive suicidal ideation.Conclusions: Although LLD is a strong determinant of suicidal ideation, other non-psychiatric factors, i.e., serum inflammation biomarkers, APOE ε4 allele, and multimorbidity, should be taken into account when evaluating a suicidal ideation phenotype in older age. [ABSTRACT FROM AUTHOR]

Background: Changes in cardiac size, myocardial mass, cardiomyocyte appearance, and, ultimately, the function of the entire organ are interrelated features of cardiac remodeling that profoundly affect patient outcomes.Objectives: This study proposes that the application of radiomics for extracting cardiac ultrasonic textural features (ultrasomics) can aid rapid, automated assessment of left ventricular (LV) structure and function without requiring manual measurements.Methods: This study developed machine-learning models using cardiac ultrasound images from 1,915 subjects in 3 clinical cohorts: 1) an expert-annotated cardiac point-of-care-ultrasound (POCUS) registry (n = 943, 80% training/testing and 20% internal validation); 2) a prospective POCUS cohort for external validation (n = 275); and 3) a prospective external validation on high-end ultrasound systems (n = 484). In a type 2 diabetes murine model, echocardiography of wild-type (n = 10) and Leptr-/- (n = 8) mice were assessed longitudinally at 3 and 25 weeks, and ultrasomics features were correlated with histopathological features of hypertrophy.Results: The ultrasomics model predicted LV remodeling in the POCUS and high-end ultrasound external validation studies (area under the curve: 0.78 [95% CI: 0.68-0.88] and 0.79 [95% CI: 0.73-0.86], respectively). Similarly, the ultrasomics model predicted LV remodeling was significantly associated with major adverse cardiovascular events in both cohorts (P < 0.0001 and P = 0.0008, respectively). Moreover, on multivariate analysis, the ultrasomics probability score was an independent echocardiographic predictor of major adverse cardiovascular events in the high-end ultrasound cohort (HR: 8.53; 95% CI: 4.75-32.1; P = 0.0003). In the murine model, cardiomyocyte hypertrophy positively correlated with 2 ultrasomics biomarkers (R2 = 0.57 and 0.52, Q < 0.05).Conclusions: Cardiac ultrasomics-based biomarkers may aid development of machine-learning models that provide an expert-level assessment of LV structure and function. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the effects of butylphthalide on cognitive deficiencies following sleep deprivation (SD).Methods: The influence of butylphthalide on cognitive function changes in SD-induced mice was evaluated. Nissl staining and HE staining were used to analyze the morphology changes of the hippocampal formation. The changes in cognitive function of SD-induced mice were detected by the Morris water maze. Inflammatory factors, apoptosis, and signal pathway-related proteins in the mice hippocampus were detected.Results: SD increased escape latency and path length for mice to reach the hidden platform, decreased the time and range of activity in the target area, and reduced the number and time for traversing the target area. Butylphthalide significantly improved the cognitive decline of SD-induced spatial exploration and learning/memory ability. Butylphthalide also decreased the degeneration of hippocampal neurone, neuronal apoptosis, and inflammatory factors in hippocampus tissue. In addition, butylphthalide activated the nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase 1 (HO-1) pathway.Conclusion: Butylphthalide alleviated SD-induced cognitive decline, neuronal apoptosis, and inflammation by activating Nrf2/HO-1 pathway. We suggested that butylphthalide may be a prospective candidate for the alleviation of cognitive deficit induced by SD. [ABSTRACT FROM AUTHOR]

Objective: Previous studies indicate that propofol can help with recovery from sleep deprivation and has anti-anxiety effects. However, the underlying neurochemical mechanism remains unclear. This study aimed to investigate the effects of dopamine transporter (DAT) in the ventral tegmental area (VTA) on sleep and anxiety recovery after propofol anesthesia in rats with 24 h total sleep deprivation (TSD).Methods: Adult male Sprague-Dawley rats were in natural sleep or sleep deprived for 24 h in a sleep deprivation rat system. The rats received propofol anesthesia (75 mg/kg, i.p.) or natural sleep. Dopamine transporter knockdown was performed by microinjection of AAV-DAT-RNAi vector. EEG was measured in each group to evaluate the subsequent sleep. The elevated plus maze test (EPMT) and open field test (OFT) were used to evaluate locomotion and anxiety level in rats. Immunofluorescence was used to verify virus location and transfection efficiency.Results: Compared with NC group, the anxiety level of Propofol group showed no significant difference, but REM sleep decreased. Compared with the TSD group, the anxiety level of the TSD + Propofol group was reduced and the sleep recovery was closer to baseline. Compared with TSD + AAV-NC group, anxiety level and sleep time increased in TSD + AAVi group, REM increased within 24 h after sleep deprivation. The sleep time of TSD + AAVi + Propofol group was between those of TSD + AAV-NC group and TSD + AAVi group. TSD + AAV-NC + Propofol group had the least sleep time and the lowest anxiety level.Conclusion: 1. Propofol did not change anxiety level in normal rats, but reduced REM sleep, while it could accelerate sleep recovery and reduce anxiety level in sleep-deprived rats. 2. In sleep deprived rats with DAT knockdown, propofol improved sleep and anxiety levels more slowly, especially producing more REM rebound, suggesting that the improvement of sleep and anxiety levels in sleep-deprived rats with propofol may be related to DAT in VTA region. [ABSTRACT FROM AUTHOR]

Purpose: Variations in many genes may lead to the occurrence of oocyte maturation defectsand female infertility. The objective was to describe newly discovered mutations in TUBB8 and ZP3, and to characterise the accompanying spectrum of phenotypes and modes of inheritance.Methods: TUBB8 and ZP3 were sequenced from genomic DNA samples extracted from peripheral blood of patients and their family members by the whole-exome sequencing. The TUBB8 and ZP3 sequences are then aligned with cryptographic software to identify rare variations. Sanger sequencing and mass spectrometry were used to validate mutations. ExAC database was used to retrieve the frequency of corresponding mutations. PolyPhen-2 and PROVEAN were analyzed for mutations using silicon.Results: We identified Three novel mutations and two known variant in TUBB8 and ZP3 associated with maturation in five families, and fertilization and developmental arrest are in these patients. These mutations include four heterozygous mutations in TUBB8 (c.730G > A, p.Gly244Ser, c.124C > G, p.Leu42Val, c.1172G > T, p.Arg391Leu and c.178G > A, p.Val60Met), and a heterozygous mutation in ZP3 (c.400G > A, p.Ala134Thr). Among them, these variants of TUBB8 were highly conserved among primates.Conclusion: As far as we know, the TUBB8 mutations detected in our study at four sites have not been reported before, and the variant of ZP3 has been published as pathogenic. Our findings extend the known mutant spectrum of TUBB8 and ZP3, and provide insights into the etiology of infertility in human women. The exact molecular mechanism has not been analyzed and should be further investigated in the future. [ABSTRACT FROM AUTHOR]

Background: There are several options available for conservative treatment of partial-thickness burns, however, reliable, affordable, and easily obtainable animal testing models are hard to find for the comparison of the different treatment methods. We aimed at developing a preclinical testing model and at comparing four treatment methods for superficial partial-thickness burns.Methods: Burn injury was induced in 90 adult male Wistar rats by placing the 130°C hot tip of a commercially obtainable soldering device for 30 s on the clipped skin of the interscapular region at a steady pressure. Skin histology was studied on days 5, 10, and 22 after the induction of the burn injury, on which days, respectively, the ratio of the not epithelialized wound (%), the extent of re-epithelialization (score), and the scar thickness (µm) were assessed. We compared 4 groups: silver-sulfadiazine cream, zinc-hyaluronan gel, silver foam dressing, and the combination of zinc-hyaluronan gel with a silver foam dressing.Results: On day 5, the induction of superficial partial-thickness burn injury was confirmed histologically in the rats. The zinc-hyaluronan gel and the combination treatment resulted in a markedly smaller ratio of the non-epithelialized area (29 ± 10% and 28 ± 13%, respectively) than silver-sulfadiazine cream (69 ± 4%; p < 0.01). On day 10, the extent of re-epithelialization was the lowest (∼0.2) in the silver-sulfadiazine cream group, while the other 3 treatments performed significantly better. The combination treatment lead to the maximal score of 2 in all rats, which was higher than in the other 3 treatment groups. On day 22, the scar thickness was the smallest in the combination treatment group (560 ± 42 µm), which was significantly less than in the silver-sulfadiazine cream group (712 ± 38 µm; p < 0.05).Conclusions: We designed and histologically confirmed a reproducible method for induction of superficial partial-thickness burns in rats for preclinical testing. In our model, the combination of zinc-hyaluronan gel with silver foam dressing was more effective than either of its components alone or than silver-sulfadiazine cream. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) play a key role in wound healing, and the advantages of pretreated MSCs in wound healing have previously been reported. In the present study, we investigated the impact of LPS pretreated human adipose-derived MSCs on skin wound healing in diabetic rats. We found that some improvements occurred through improving angiogenesis. Then, we scrutinized the impact of lipopolysaccharide (LPS) treatment on human adipose-derived MSCs in a high-glucose (HG) medium, as an in vitro diabetic model. In vivo findings revealed significant improvements in epithelialization and angiogenesis of diabetic wounds which received LPS pre-MSCs. Particularly, LPS pre-MSCs-treated diabetic wounds reached considerably higher percentages of wound closure. Also, the granulation tissue of these wounds had higher pronounced epithelialization and more vascularization compared with PBS-treated and MSCs-treated diabetic ones by CD31, VEGF, CD90, collagen 1, and collagen 3 immunostaining. Western-blots analyses indicated that LPS pre-MSCs led to the upregulation of vascular endothelial growth factor (VEGF) and DNMT1. In addition, significantly higher cell viability (proliferation/colonie), and elevated VEGF and DNMT1 protein expression were observed when MSCs were treated with LPS (10 ng/ml, 6 h) in HG culture media. Based on these findings, it is suggested that LPS pre-MSCs could promote wound repair and skin regeneration, in some major processes, via the improvement of cellular behaviors of MSCs in the diabetic microenvironment. The beneficial advantages of LPS treated with mesenchymal stem cells on wound healing may lead to establishing a novel approach as an alternative therapeutic procedure to cure chronic wounds in diabetic conditions. [ABSTRACT FROM AUTHOR]

The aim of this study was to verify the effects of ultrasound on dorsal root ganglion (DRG) neurons at the injury site in a rat model of sciatic nerve crush injury. We evaluated the mRNA expression of neurotrophic and pro-inflammatory factors by quantitative reverse transcription polymerase chain reaction 7 and 14 d post-injury. We also evaluated the protein levels of brain-derived neurotrophic factor (BDNF) 7 and 14 d post-injury. Axon regeneration and motor function analyses were performed 21 days after injury to confirm the facilitative effect of ultrasound on nerve regeneration. In the ultrasound group, BDNF and interleukin-6 mRNA expression of the DRG was significantly reduced 7 d post-injury. Compared with the sham group, the BDNF protein expression of the DRG in the ultrasound group remained at a higher level 14 d post-injury. Motor function, myelinated fiber density and myelin sheath thickness were significantly higher in the ultrasound group than in the sham group 21 d post-injury. These results indicate that ultrasound therapy at the injury site promotes nerve regeneration and modulates gene and protein expression in the DRG of a rat model of a sciatic nerve crush injury. [ABSTRACT FROM AUTHOR]

Objective: Head and neck surgeries may cause changes in the nasal airflow, and radiotherapy irreversibly damages paranasal sinus epithelial cells. Some chemotherapeutic drugs have been reported to negatively affect airway ciliary activity in mice, and chronic rhinosinusitis could be an adverse effect of head and neck cancer (HNC) treatment. To evaluate whether HNC treatment is a risk factor for developing sinonasal mucosal thickening that may reflect paranasal sinus inflammation, we compared pre- and post-treatment paranasal sinus computed tomography (CT) images of patients treated for HNC at a single university hospital.Methods: The patients who received curative treatment for HNC (oral, pharyngeal, and laryngeal cancers) and started receiving first-line therapy between January 2015 and December 2019 were included. Data on age, sex, primary lesion, clinical stage, treatment, smoking history, drinking history, comorbidities (diabetes and chronic lung disease), and pre- and post-treatment (three months and one year after the final treatment) paranasal sinus CT images were analyzed from medical records. Pre- and post-treatment paranasal sinus CT images were scored using the Lund-Mackay (LM) staging system.Results: In total, 245 patients participated in this study. Three months after the final treatment, 80.4% of patients had no change in their total LM scores (p=0.621). Almost 80% of patients who underwent total laryngectomy also had no change in their total LM scores (p=0.833). One-third of patients with nasopharyngeal cancer (NPC) had worse LM scores after treatment (5/15), although no significant difference was observed (p=0.171). None of the various factors collected were significantly related to changes in LM scores three months after the completion of treatment. One year after the final treatment, 211 patients were included and no significant changes in the pre-and post-LM scores were observed in the same analyses, while changes in LM scores were significantly different between T categories (T1-2 vs. T3-4) (p=0.020).Conclusion: We found no significant changes in the LM scores after HNC treatment in all the patients, which implies that HNC treatment may not be an apparent risk factor for sinonasal mucosal inflammation. [ABSTRACT FROM AUTHOR]

Various studies have reported discordant results on the magnitude and direction of burn-induced coagulopathy (BIC), which has recently been associated with multiple organ dysfunction syndrome (MODS) and death. The increased mechanistic understanding of BIC is due, in part, to novel assays that have expanded the armamentarium beyond traditional tests like PT and aPTT. Still, BIC is a dynamic process, and the progression is difficult to define in the thermally-injured. To this end, we aimed to enhance the understanding of burn-induced coagulation abnormalities by employing functional assessments of platelet aggregation, viscoelastic kinetics, and thrombin generation in an extensive burn model in swine. Anesthetized Yorkshire pigs sustained 40% total body surface area (TBSA) full-thickness contact burns and recovered in metabolic cages. Blood was collected at baseline (BL), as well as 6, 24, and 48 h after injury. A significant effect of burn (P < 0.0001) was seen on platelets, with mild thrombocytopenia apparent at 24 h. While slight decreases in aPTT were not significant, rotational thromboelastometry (ROTEM) analysis revealed hypercoagulation 6 and 24 h after burn by a decreased clotting time. Maximum clot firmness increased after burn, but was not statistically significant until 48 h. Hypercoagulation was not supported by platelet aggregation, as the response to ADP was greatly and persistently diminished, and the response to collagen was unchanged. Endogenous thrombin potential was significantly reduced at 6 and 24 h after burn (P < 0.0001), and also correlated with a number of ROTEM parameters and collagen-induced platelet aggregation. In contrast, PT was not correlated with other measured parameters. Taken together, novel coagulation parameters may be more sensitive than PT in characterizing coagulopathy in the setting of burns. The data presented herein makes initial strides to report the natural history of several of these variables over time in a large animal model of extensive burns, indicating early hypercoagulability followed by hypocoagulation. Future work will elucidate the effects of standard of care. [ABSTRACT FROM AUTHOR]

Introduction: Delays in treatment of burn injuries can lead to significant morbidity, loss of function, and poor aesthetic appearance. Preventing conversion from partial- to full-thickness burns may help mitigate these sequelae. The pathophysiology of burn wound conversion remains unknown, but an overactive immune response is thought to be implicated. The purpose of this study was to determine whether downregulating the immune response via tacrolimus can decrease burn wound conversion.Methods: Assembly of the microfluidic hydrogels was achieved by embedding microfibers within a hydrogel scaffold composed of a gelatin-alginate blend. Tacrolimus stock solution for intraperitoneal injection was made by re-suspending powdered tacrolimus in DMSO at 10 mg/mL. 24 young (2-4 months) and 24 old (>16 months) mice were given partial thickness burns. The treatment cohort received either tacrolimus ointment with a hydrogel dressing (6 young and 6 old) or an intraperitoneal injection of a tacrolimus solution (6 young and 6 old), while the control cohort only received either only the microcapillary hydrogel dressing or an intraperitoneal injection of saline. Mice were euthanized at day 3 after injury and skin samples were taken. Burn depth was evaluated using Vimentin immunostaining.Results: In old mice, intraperitoneal injection of tacrolimus was able to significantly reduce burn wound depth compared to intraperitoneal injection of saline (p = 0.011). Similarly in old mice, topical hydrogel with tacrolimus was able to significantly reduce burn wound depth compared to hydrogel alone (p < 0.001). Topical hydrogel with tacrolimus was able to mitigate the detrimental effects of older age on wound conversion, such that burn wounds of older mice treated with tacrolimus hydrogel dressing had similar burn depths as younger mice (p = 0.240).Conclusions: Utilizing a combination treatment of tacrolimus and microcapillary hydrogel is able to rescue the negative effects of aging and prevent partial- to full-thickness burn wound conversion. Hopefully these findings will encourage deeper investigation into the possible therapeutic advantages of utilizing immunosuppressive agents to decrease morbidity after burn injuries. Future research will need to specifically investigate IL-2 as an inhibitory target in the acute inflammatory cascade of burn injury. [ABSTRACT FROM AUTHOR]

Objective: The high levels of oxidative stress and apoptosis of pancreatic islet cells after severe burns lead to the dysfunction of islets and glucose metabolism disorders. Silent information regulator of transcription 1 (SIRT1) can decrease oxidative stress and apoptosis of islets in diabetes mellitus. This study aimed to investigate the role of SIRT1 on pancreatic islets and whether nicotinamide mononucleotide (NMN) can impact the function of pancreatic islets after severe burns.Methods: A 30% total body surface area full-thickness burn model was established using male C57BL/6 mice, and mice were randomized into sham group, burn group, burn + NMN group and burn + NMN + EX-527 group. The concentration of nicotinamide adenine dinucleotide (NAD), the expression of SIRT1, apoptosis induction, mitochondrial function and related signalling pathways of pancreatic islets at 24 h after severe burns were tested.Results: Severe burns led to decreased NAD level and SIRT1 expression of pancreatic islets, increased apoptosis rate, and mitochondrial dysfunction of pancreatic islets. NAD repletion by NMN and upregulation of SIRT1 expression reduced the phosphorylation and acetylation levels of NF-κB p65 and burn-induced apoptosis. Meanwhile, the mitochondrial function of islets was rescued by NMN treatment through the SIRT1/UCP2 axis and SIRT1/PGC1-α axis. In addition, the fasting blood glucose decreased and glucose-stimulated insulin secretion was improved with NMN treatment after severe burns. This protective effect of NMN could be abolished by EX-527, the inhibitor of SIRT1.Conclusion: NMN can increase the concentration of NAD+ of pancreatic islets and regulate SIRT1 and its downstream targets, thereby reducing apoptosis, maintaining mitochondrial function and improving pancreatic islet function after severe burn injury. [ABSTRACT FROM AUTHOR]

Background: Among the zones of coagulation, hyperemia and stasis that occur in the burned area, the most intense metabolic process and the highest sensitivity to recovery with treatment is the zone of stasis.This metabolic process is related to how well the tissues in the zone of stasis can cope with oxidative stress. If the tissues in the zone of stasis are saved, the burn area will potentially heal faster and with less scar. In this study, we examined the effects of taurine amino acids and apocynin molecules on saving the tissues in the burn zone of stasis.Methods: The study was conducted with 48 rats. The burn zone of stasis was created according to the pattern previously described in the literature as comb burn model. In the 21-day study, biopsies were taken for histological examination on the 3rd, 7th and 21st days of the study. In addition, macroscopic photographic analysis was performed. Biopsies were taken for biochemical analysis on the 21st day. Histologically, inflammation, reepithelialization, and collagenization were evaluated, and the CD34 immunoreactivity was analysed. Biochemically, CAT, SOD, tGSH, TAS, TOS, MDA and PPC values were determined.Results: In the histological examination, on the 3rd, 7th and 21st days, inflammation was found to be reduced in the groups given taurine and apocynin on the 3rd day. On the 7th day, better reepithelialization and collagenization were observed in the group given taurine. Significant reepithelialization, collagenization and hair follicle development were observed in the groups given taurine and apocynin on the 21st day. In the biochemical analysis, the effects of apocynin on antioxidant enzymes were determined to be prominent. While we found no significant difference on the 3rd and 7th days in the photographic analysis, taurine and apocynin were observed to act synergistically on the 21st day and significantly reduced the burned areas.Conclusion: On the 3rd day, taurine and apocynin prevented inflammation, the effects of taurine in the zone of stasis in the early period (7th day) are more pronounced, the effect of apocynin on antioxidant enzymes is more pronounced. In the late period (21st day), taurine and apocynin were found to be more effective in saving the zone of stasis by creating a synergistic effect. [ABSTRACT FROM AUTHOR]

Autologous skin cell suspensions (ASCS) can treat burns of varying depths with the advantage of reduced donor site wound burden. The current standard primary dressing for ASCS is a nonabsorbant, non-adherent, perforated film (control) which has limited conformability over heterogeneous wound beds and allows for run-off of the ASCS. To address these concerns, a novel spray-on polymer formulation was tested as a potential primary dressing in porcine deep partial thickness (DPT) and full thickness (FT) wounds. It was hypothesized that the polymer would perform as well as control dressing when evaluating wound healing and scarring. DPT or FT wounds were treated with either a spray-on poly(lactic-co-glycolic acid) (PLGA) and poly(lactide-co-caprolactone) (PLCL) formulation or control ASCS dressings. Throughout the experimental time course (to day 50), we found no significant differences between polymer and control wounds in % re-epithelialization, graft-loss, epidermal or dermal thickness, or % dermal cellularity in either model. Pigmentation, erythema, elasticity, and trans-epidermal water loss (TEWL), were not significantly altered between the treatment groups, but differences between healing wounds/scars and un-injured skin were observed. No cytotoxic effect was observed in ASCS incubated with the PLGA and PLCL polymers. These data suggest that the novel spray-on polymer is a viable option as a primary dressing, with improved ease of application and conformation to irregular wounds. Polymer formulation and application technique should be a subject of future research. [ABSTRACT FROM AUTHOR]

Background: Adipose-derived mesenchymal stem cells (adMSCs) are suggested as potential tools for the treatment of regenerative diseases, including tissue repair. This study aimed to explore the function of adMSC-derived apoptotic bodies in skin wound healing and the molecules of action.Methods: The acquired adMSCs and their-derived apoptotic bodies were identified. A murine model of full-thickness skin wounds was treated with apoptotic bodies. The wound healing process of mice and the pathological changes in wound tissues were examined. Ana-1 macrophages were treated with lipopolysaccharide (LPS) and apoptotic bodies for in vitro experiments. Polarization of macrophages was examined by immunofluorescence staining of the specific biomarkers and ELISA kits. Dermal microvascular endothelial cells (DMECs) or dermal fibroblasts (DFs) were co-cultured with apoptotic bodies or the LPS- and apoptotic bodies-treated Ana-1 cells. Downstream molecules mediated by apoptotic bodies were screened by microarray and bioinformatic analyses.Results: Apoptotic bodies treatment accelerated skin wound healing in mice and promoted formation of granulation tissues and blood vessels in wound tissues. Apoptotic bodies treatment induced M2 polarization of macrophages. The angiogenesis ability of DMECs, and the viability and migration of DFs were increased when co-cultured with the apoptotic bodies-treated Ana-1 cells. MicroRNA (miR)-21-5p was abundantly expressed in ABs, and kruppel like factor 6 (KLF6) mRNA was confirmed as a target of miR-21-5p. Overexpression of KLF6 reduced M2 polarization of macrophages and blocked the promoting effect of apoptotic bodies on wound healing in vitro and in vivo.Conclusion: miR-21-5p carried by adMSC-derived apoptotic bodies targets KLF6 to induce M2 polarization of macrophages and augment skin wound healing. [ABSTRACT FROM AUTHOR]

Background: Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral infection, present across Africa and Eurasia, which might pose a cryptic public health problem in Uganda. We aimed to understand the magnitude and distribution of CCHF risk in humans, livestock and ticks across Uganda by synthesising epidemiological (cross-sectional) and ecological (modelling) studies.Methods: We conducted a cross-sectional study at three urban abattoirs receiving cattle from across Uganda. We sampled humans (n = 478), livestock (n = 419) and ticks (n = 1065) and used commercially-available kits to detect human and livestock CCHF virus (CCHFV) antibodies and antigen in tick pools. We developed boosted regression tree models to evaluate the correlates and geographical distribution of expected tick and wildlife hosts, and of human CCHF exposures, drawing on continent-wide data.Findings: The cross-sectional study found CCHFV IgG/IgM seroprevalence in humans of 10·3% (7·8-13·3), with antibody detection positively associated with reported history of tick bite (age-adjusted odds ratio = 2·09 (1·09-3·98)). Cattle had a seroprevalence of 69·7% (65·1-73·4). Only one Hyalomma tick (CCHFV-negative) was found. However, CCHFV antigen was detected in Rhipicephalus (5·9% of 304 pools) and Amblyomma (2·9% of 34 pools) species. Modelling predicted high human CCHF risk across much of Uganda, low environmental suitability for Hyalomma, and high suitability for Rhipicephalus and Amblyomma.Interpretation: Our epidemiological and ecological studies provide complementary evidence that CCHF exposure risk is widespread across Uganda. We challenge the idea that Hyalomma ticks are consistently the principal reservoir and vector for CCHFV, and postulate that Rhipicephalus might be important for CCHFV transmission in Uganda, due to high frequency of infected ticks and predicted environmental suitability.Funding: UCL Global Challenges Research Fund (GCRF) and Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET) funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) under the EU Horizon 2020 Framework Programme for Research and Innovation. [ABSTRACT FROM AUTHOR]

Objectives: Preeclampsia is a life-threatening disorder of pregnancy unique to humans. Poor placentation in the first trimester of pregnancy is widely accepted to be an underlying cause of preeclampsia. Galectin-7 is abnormally elevated in chorionic villous samples and serum from women that subsequently develop pre-term preeclampsia. Administration of exogenous galectin-7 to pregnant mice causes preeclampsia-like features (hypertension, proteinuria), associated with dysregulation of the renin-angiotensin system (RAS). In this study investigated the mechanism by which galectin-7 induces alterations to tissue RAS homeostasis and ROS production. We hypothesized that galectin-7 induces alterations in the production of either placental RAS or NADPH oxidases (or both) to drive the dysregulated RAS and ROS production seen in preeclampsia.Study Design: Mated female mice (n = 5-6/group) received single (embryonic day [E]12/13) or multiple (E8-12) subcutaneous injections of 400 μg/kg/day galectin-7 or vehicle control and killed on E13 or E18. Human first trimester placental villous and decidual tissue (n = 11) was cultured under 8 % oxygen with 1 µg/mL galectin-7 or vehicle control for 16 h.Results: Galectin-7 administration to pregnant mice impaired placental labyrinth formation, suppressed circulating aldosterone and altered placental RAS (Agt, Renin) and NADPH oxidase (Cyba, Cybb and Icam1) mRNA expression. In vitro, galectin-7 regulated human placental villous RAS (AGT) and NADPH oxidase (CYBA, ICAM1 and VCAM1) mRNA expression.Conclusions: Overall, galectin-7 likely drives hypertension in preeclampsia via its direct regulation of multiple pathways associated with preeclampsia in the placenta. Galectin-7 may therefore be a therapeutic target to improve placental function and prevent preeclampsia. [ABSTRACT FROM AUTHOR]

Objectives: To assess the association between altered expression of caveolin-1 and p53/p21, as indicatives of cellular senescence, in preeclamptic placenta.Study Design: Placental tissues and serum were collected from rats (Sham and reduced uterine perfusion pressure group) at 18.5 days post coitum and humans (normotensive pregnant and preeclampsia groups). The concentration and expression of caveolin-1 were measured in the collected tissues, and the correlation between p53 and p21 expression was evaluation.Main Outcome Measures: Placental mRNA expression and serum concentration of caveolin-1 were measured using qRT-PCR and ELISA, respectively. Altered expressions of caveolin-1 and p53/p21 were revealed and quantified by immunohistochemistry. The association between these changes was investigated using correlation analysis.Results: Placental mRNA expressions and serum concentrations of caveolin-1 were significantly decreased in reduced uterine perfusion pressure and preeclampsia groups. The expressions of caveolin-1 and p53/ p21 were significantly altered in placenta complicated with preeclampsia. Correlation analysis revealed a significant inverse association between changes in caveolin-1 and p53/p21. Subsequently, these results were obtained by investigating the preeclampsia onset time.Conclusion: These results revealed that the expression of caveolin-1 profoundly decreases in the placenta and serum of preeclampsia. These factors contribute to the mechanism of accelerated cellular senescence in placenta, which is one of the various etiologies of preeclampsia. [ABSTRACT FROM AUTHOR]

Introduction: Accumulating epidemiological studies support that Vitamin D deficiency is associated with the pathogenesis of preeclampsia. However, it is unknown whether vitamin D can be used as a treatment for preeclampsia. This study aimed to explore whether vitamin D supplementation could improve the rat model of preeclampsia.Methods: LPS was used to establish a rat model of preeclampsia. Inflammatory cytokines were examined by QRT-PCR and ELISA assays, and the concentration of sfit-1 and NO was assessed by ELISA. Analyzing the pathological features of the placenta with hematoxylin-eosin. The spatial learning and memory abilities of offspring were evaluated by the Morris water maze. Immune histology and western blot were performed to evaluate the expression levels of inflammatory pathway-associated Factor and vascular endothelium-associated Factor in the placenta.Results: Vitamin D treatment reduced the blood pressure and urine protein of PE model rats, alleviated pathological damage to the placenta and pregnancy outcomes, and protected PE offspring from impaired memory and learning abilities. Moreover, TLR4 signaling pathway in the placenta was inhibited. Furthermore, vitamin D supplementation increased the expression of endothelial growth factor and vascular relaxing factor, and there was no significant difference compared with the control group.Discussion: We generated the result that Vitamin D supplementation significantly improved the phenotype of preeclampsia and adverse pregnancy outcome caused by an abnormal inflammatory reaction and endothelial dysfunction in the placenta, and improved the learning and cognitive ability of offspring. [ABSTRACT FROM AUTHOR]

Background: The putative mechanisms underlying the efficacy of the US Food and Drug Administration-approved antipsychotic drug paliperidone for the treatment of schizophrenia deserve additional investigation, which is the aim of the present animal study.Methods: The behavioral activities of mice were recorded in the open field test and light-dark box test. The effects of paliperidone on MK-801-induced neuronal damage in the prefrontal cortex were tested by flow cytometry, TUNEL staining assays, and ROS staining assays. The neuroprotective effects of paliperidone on neural dendrites and synapses were evaluated using Golgi staining and Sholl analysis. An adenovirus vector containing a Ca2+ indicator was used to monitor the calcium ion concentration in the prefrontal cortex. The expression levels of protein phosphatase 2A (PP2A) and phosphatase and tensin homolog (PTEN) were investigated using Western blotting.Results: The data showed that MK-801 caused stereotyped behavior in mice and induced synaptic damage and dendritic spine impairment compared with the control, whereas paliperidone ameliorated these changes. Moreover, paliperidone reversed MK-801-induced decreases in PP2A and PTEN levels in prefrontal cortical neurons. Furthermore, in primary cultured cortical neurons and HT-22 cells, paliperidone inhibited cell apoptosis caused by MK-801. In particular, pretreatment with the PP2A inhibitor LB-100 significantly restrained the protective effects of paliperidone on MK-801-treated neurons and on locomotor activity and stereotypical behavior of mice.Limitations: Whether other proteins are involved in this pathway and how the pathway works have not been revealed.Conclusion: Our data show that paliperidone alleviates neuronal damage induced by MK-801 via the PP2A/PTEN pathway. [ABSTRACT FROM AUTHOR]

Purpose: Synchrotron-generated microbeam radiation therapy (MRT) represents an innovative preclinical type of cancer radiation therapy with an excellent therapeutic ratio. Beyond local control, metastatic spread is another important endpoint to assess the effectiveness of radiation therapy treatment. Currently, no data exist on an association between MRT and metastasis. Here, we evaluated the ability of MRT to delay B16F10 murine melanoma progression and locoregional metastatic spread.Methods and Materials: We assessed the primary tumor response and the extent of metastasis in sentinel lymph nodes in 2 cohorts of C57BL/6J mice, one receiving a single MRT and another receiving 2 MRT treatments delivered with a 10-day interval. We compared these 2 cohorts with synchrotron broad beam-irradiated and nonirradiated mice. In addition, using multiplex quantitative platforms, we measured plasma concentrations of 34 pro- and anti-inflammatory cytokines and frequencies of immune cell subsets infiltrating primary tumors that received either 1 or 2 MRT treatments.Results: Two MRT treatments were significantly more effective for local control than a single MRT. Remarkably, the second MRT also triggered a pronounced regression of out-of-radiation field locoregional metastasis. Augmentation of CXCL5, CXCL12, and CCL22 levels after the second MRT indicated that inhibition of melanoma progression could be associated with increased activity of antitumor neutrophils and T-cells. Indeed, we demonstrated elevated infiltration of neutrophils and activated T-cells in the tumors after the second MRT.Conclusions: Our study highlights the importance of monitoring metastasis after MRT and provides the first MRT fractionation schedule that promotes local and locoregional control with the potential to manage distant metastasis. [ABSTRACT FROM AUTHOR]

Purpose: The majority of cancer-related deaths are attributed to metastasis rather than localized primary tumor progression. However, the factors that regulate the premetastatic niche (PMN) and metastasis have not yet been clearly elucidated. We investigated the antimetastatic effects of irradiated tumor cell-derived microparticles (RT-MPs) and highlighted the role of innate immune cells in PMN formation.Methods and Materials: Mice were treated 3 times with isolated RT-MPs, followed by tumor cell injection via the tail vein. The hematoxylin and eosin staining was performed to assess the number of tumor nodules in the lungs, and in vivo luciferase-based noninvasive bioluminescence imaging was conducted to detected tumor burden. The mechanisms of RT-MPs mediated PMN formation was evaluated using flow cytometry, transwell assay, and reverse transcription-polymerase chain reaction.Results: RT-MPs inhibited tumor cell colonization in the lungs. Neutrophils phagocytosed RT-MPs and secreted CCL3 and CCL4, which induced monocytes chemotaxis and maturation into macrophages. RT-MPs promoted the transition of neutrophils and macrophages into antitumor phenotypes, hence inhibiting cancer cell colonization and proliferation.Conclusions: RT-MPs inhibited PMN formation and lung metastasis in a neutrophil- and macrophage-dependent but T cell-independent manner. [ABSTRACT FROM AUTHOR]

Glioma is the most common and most invasive primary central nervous system tumour, and it is urgent to develop new specific therapeutic targets. Studies have confirmed that epithelial-derived tumour cells promote tumour cell proliferation and metastasis by secreting a large number of immunoglobulins (Igs), but the role of tumour-derived Igs in glioma has never been reported. The Gene Expression Profiling Interactive Analysis and Chinese Glioma Genome Atlas databases were used to analyse the Ig transcription and its correlation with the prognosis of patients with glioma. Immunohistochemistry and immunofluorescence were used to detect the protein expression of IgG and IgM in the glioma tissues of patients and glioma cell lines. When IgG was knocked down by small interfering RNA or knocked out by CRISPR-Cas9, the function of proliferation and migration of glioma cells were analysed by CCK-8, clone formation, wound healing, and transwell assays. Changes in proteins and their phosphorylation in signalling pathways were detected by western blotting. The nude mouse subcutaneous tumour-bearing model was established to analyse the effect of IgG in vivo. The transcriptional level of IgG was pretty high in glioma tissues and was positively correlated with high WHO grade, recurrence, and poor prognosis. The expression of IgG and IgM was found in tumour tissues and human glioma cell lines U87 and U251, and the main expression form was secreted. Decreased IgG inhibited the proliferation and migration of glioma cells. Knockout or knockdown of IgG downregulated the phosphorylation of the key molecules in the MAPK and PI3K/Akt pathway through the HGF/SF-Met or FAK/Src pathway. In vivo tumourigenesis mouse model confirmed that reduced IgG expression inhibited glioma growth. Ig was expressed in glioma tissues and cell lines, and a high expression level predicted a poor prognosis of patients. Glioma-derived IgG promoted glioma cell proliferation and migration through the HGF/SF-Met or FAK/Src pathway. • Both glioma tissues and cell lines expressed immunoglobulin. • Glioma-derived IgG promoted proliferation and migration of glioma cells. • Reduction of IgG expression inhibited the growth of gliomas in mice. • Glioma-derived IgG may be a potential new target for glioma immunotherapy. [ABSTRACT FROM AUTHOR]

Western-style obesity-promoting diets are associated with increased inflammation, higher disease incidence and mortality. In contrast, plant-based diets (PBDs), which incorporate large amounts of vegetables and fruit, legumes, whole grains and only a small amount of meat, are generally associated with better health and lower mortality. This narrative review summarizes the evidence on health and life span in adults adhering to PBDs and discusses the potentially longevity-promoting mechanism of PBDs as well as limitations due to nutrient deficiencies. Epidemiologic studies consistently report lower mortality rates in adults who adhering to PBDs when compared with people whose diet regularly includes meat. PBDs are associated with many health benefits, such as improved metabolic and inflammatory profile. In turn, the incidence of cardiovascular disease is lower in adults consuming PBDs, which contributes to their better health. The health-promoting effects of PBDs are still not entirely clear but most likely multifactorial and include modulation of the gut microbiome. The interest in possible longevity-promoting mechanisms of PBDs has increased in recent years, as many characteristics of PBDs such as protein restriction and restriction of certain amino acids are known to extend the life span. While there is ample evidence from animal studies, large-scale human studies, which also provide insight into the specific mechanisms of the effect of PBDs on longevity, are missing. However, due to the lower protein content of PBDs, there appears to be an age limit for the anticipated health effects, as adults over 65 require larger amounts of protein. [ABSTRACT FROM AUTHOR]

Introduction: Traumatic brain injuries (TBI) represent a significant percentage of critical injuries in military conflicts. Following injury, wounded warfighters are often subjected to multiple aeromedical evacuations (AE) and associated hypobaria, yet the impact in TBI patients remains to be characterized. This study evaluated the impact of two consecutive simulated AEs in a fluid-percussion TBI model in swine to characterize these effects.Methods: Following instrumentation, anesthetized Yorkshire swine underwent a frontal TBI via fluid-percussion. A hypobaric chamber was then used to simulate AE at simulated cabin pressure equivalent to 8000ft (hypobaria) in a 6 h initial flight on day 3, followed by a 9 h flight on day 6, and were monitored for 14 days. Animals in the normobaria group were subjected to the same steps at sea level while Sham animals in both groups were instrumented but not injured. Parameters measured included physiologic response, intracranial pressure (ICP), hematology, chemistry, and serum cytokines. Histopathology of brain, lung, intestine, and kidney was performed, as well as fluorojade staining to evaluate neurodegeneration. All animals were divided into sub-groups by block randomization utilizing a 2-way ANOVA to analyze independent variables.Results: Survival was 100% in all groups. Physiologic parameters were largely similar across groups as well during both 6 and 9 h AE. Animals exposed to hypobaria in both the TBI and Sham groups had elevated heart rate (HR) during the 6 h flight (p<0.05). Three animals in the TBI hypo group demonstrated leukocytosis with histologic evidence of meningeal inflammatory response. Expression of serum cytokines was low across all groups. No significant neuronal degeneration was identified in areas away from the site of injury.Conclusion: Aeromedical evacuation in swine was not associated with significant differences in physiologic measures, cytokine expression or levels of neuronal degeneration. Histological examination revealed higher risk of meningeal inflammatory response and leucocytosis in swine exposed to hypobaria. [ABSTRACT FROM AUTHOR]

The mechanical properties and microstructure of brain tissue, as its two main physical parameters, could be affected by mechanical stimuli. In previous studies, microstructural alterations due to mechanical loading have received less attention than the mechanical properties of the tissue. Therefore, the current study aimed to investigate the effect of ex-vivo mechanical forces on the micro-architecture of brain tissue including axons and glial cells. A three-step loading protocol (i.e., loading-recovery-loading) including eight strain levels from 5% to 40% was applied to bovine brain samples with axons aligned in one preferred direction (each sample experienced only one level of strain). After either the first or secondary loading step, the samples were fixed, cut in planes parallel and perpendicular to the loading direction, and stained for histology. The histological images were analyzed to measure the end-to-end length of axons and glial cell-cell distances. The results showed that after both loading steps, as the strain increased, the changes in the cell nuclei arrangement in the direction parallel to axons were more significant compared to the other two perpendicular directions. Based on this evidence, we hypothesized that the spatial pattern of glial cells is highly affected by the orientation of axonal fibers. Moreover, the results revealed that in both loading steps, the maximum cell-cell distance occurred at 15% strain, and this distance decreased for higher strains. Since 15% strain is close to the previously reported brain injury threshold, this evidence could suggest that at higher strains, the axons start to rupture, causing a reduction in the displacement of glial cells. Accordingly, it was concluded that more attention to glial cells' architecture during mechanical loading may lead to introduce a new biomarker for brain injury. [ABSTRACT FROM AUTHOR]

Introduction: Proinflammatory cytokines released from nerve endings and surrounding injured tissue after nerve damage can prolong the inflammation process, delay nerve healing or result in poor quality nerve healing. In this case, due to the loss of function in the muscles innervated by the damaged nerve, the patient may have neurological and functional difficulties which may reduce the patient's quality of life and create an economic burden. Although the attempts of many pharmacological agents to heal crush injury of peripheral nerves have been recorded in literature, a drug that can provide adequate recovery of the crushed nerve and can be applied in daily life has not been defined as yet. This study aimed to assess the effects of calcium dobesilate on sciatic nerve crush injury in a rat model.Methods: A total of 26 male Wistar albino rats were separated into four groups as follows: CONTROL group (healthy subjects, n=6); SHAM group (crush injury was created, n=6); MP group (after created crush injury, methylprednisolone was administered, n=7); and CAD group (after created crush injury, calcium dobesilate was administered, n=7). A crush injury was created, then the electrophysiological findings and sciatic nerve functional index (SFI) were recorded before euthanasia. After the euthanasia of all the rats, samples of the crushed nerve and gastrocnemius muscle were evaluated histopathologically, immunohistochemically, and biochemically.Results: Both pharmacological agents were histopathologically effective in axon regeneration and repair. Calcium dobesilate did not preserve total muscle mass but was seen to prevent atrophy microscopically. Immunohistochemistry and biochemistry results showed that calcium dobesilate and methylprednisolone had anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-autophagic activity in the crushed sciatic nerve. Neither calcium dobesilate nor methylprednisolone improved the nerve conductance level. SFI values obtained on day 30 from the CAD group were numerically closer to the values of the healthy animals but not at a statistically significant level.Conclusion: The study results demonstrated that calcium dobesilate could suppress inflammatory processes and provide histopathological and functional improvements in the injured nerve in rats. Therefore, further clinical studies are recommended to investigate in detail the therapeutic effects of calcium dobesilate on peripheral nerve crush injury. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral nerve injury due to animal bite is a rare phenomenon. Most animal bites are from dogs. Monkey bites constitute a common risk, second only to dog bites, among travelers. Peripheral nerve injuries may occur due to a combination of monkey's strong jaws and sharp long teeth penetrating deep into the soft tissues. Such injuries are associated with increased perineural fibrosis. Human amniotic membrane (HAM) wrap around the nerve repair site reduces fibrotic response, prevents adhesions and scar formation thereby improving outcome. We report a case of "High Radial nerve palsy due to monkey bite, treated by neurorrhaphy with HAM wrap".Method: A 3-year old boy presented with wrist drop, and inability to extend the fingers and thumb of his right dominant hand, following a monkey bite over the distal arm. The diagnosis of high radial nerve injury was corroborated by high frequency ultrasound and electrodiagnostic studies. On exploration the radial nerve was found to be transected. An end to end repair was performed, with HAM wrap around the neurorrhaphy.Results: Wrist dorsiflexion recovered at 2.5 months followed by active finger and thumb extension at 4 months with no infection or immune rejection.Conclusion: Nerve regeneration in our patient occurred at a faster rate as compared to the conventional 1 mm/day. This could be attributed to decreased perineural fibrosis, improved neurotropism due to the HAM wrap and neuronal plasticity in young brain in addition, the patient being a small child having better regenerative ability in comparison to an adult. [ABSTRACT FROM AUTHOR]

Background: In this study we investigated the therapeutic potential of angiotensin II pathway inhibitors in attenuating post-surgical adhesion band formation in tendon injury.Method: We assigned 30 Wistar albino rats to 5 groups, including negative control, positive control, sham, Telmisartan- and Enalapril-treated groups (n=6). Telmisartan and Enalapril at a dose of 10 mg/kg were administered intraperitoneally for 21 days. Hematoxylin-Eosin, and Masson's trichrome staining were used to measure the inflammatory cell accumulation and collagen deposition in the Achilles tendon tissue sections. Oxidative stress markers were analyzed in tissue samples by spectrophotometric methods. Properties of Achilles tendon adhesions were compared based on Tang and Ishiyama scoring systems in the presence and absence of angiotensin II pathway inhibitors.Results: Telmisartan and Enalapril reduced severity, length, and density of surgical-induced tendon adhesion at site of injury (***p < 0.001). Our results showed that administration of angiotensin II pathway inhibitors decreased infiltration of inflammatory cells to the injured area (*p < 0.05) and suppressed inflammation by regulating oxidative stress markers including MDA (***p < 0.001), total thiol (***p < 0.001), CAT (***p < 0.001), and SOD (***p < 0.001), in post-operative Achilles tendon tissues. Significant lower collagen deposition and formation of fibrotic tissues was seen in Telmisartan- and Enalapril-treated groups as detected by Masson's trichrome staining which correlated with a decrease in quantity (**p < 0.01) and grading of fibrosis score (***p < 0.001), in adhesive tissues. Moreover, inhibition of angiotensin II pathway could also ameliorate mechanical properties including ultimate load (***p < 0.001), and ultimate stress (*p < 0.05) in injured Tendons.Conclusion: Our results showed that ssuppression of inflammation and fibrosis are two mechanisms by which Telmisartan and Enalapril elicit potent protective responses post Achilles tendon injuries. [ABSTRACT FROM AUTHOR]

This study investigated induction of pulmonary capillary hemorrhage (PCH) in neonatal pigs (piglets) using three different machines: a GE Venue R1 point-of-care system with C1-5 and L4-12t probes, a GE Vivid 7 Dimension with a 7L probe and a SuperSonic Imagine machine with an SL15-4 probe and shear wave elastography (SWE). Female piglets were anesthetized, and each was mounted vertically in a warm bath for scanning at two or three intercostal spaces. After aiming at an innocuous output, the power was raised for a test exposure. Hydrophone measurements were used to calculate in situ values of mechanical index (MIIS). Inflated lungs were removed and scored for PCH area. For the C1-5 probe at 50% and 100% acoustical output (AO), a PCH threshold of 0.53 MIIS was obtained by linear regression (r2 = 0.42). The L4-12t probe did not induce PCH, but the 7L probe induced zones of PCH in the scan planes. The Venue R1 automated B-line tool applied with the C1-5 probe did not detect PCH induced by the C1-5 probe as B-line counts. However, when PCH induced by C1-5 and 7L exposures were subsequently scanned with the L4-12t probe using the automated tool, B-lines were counted in association with the PCH. The SWE induced PCH at push-pulse positions for 3, 30 and 300 s of SWE with PCH accumulating at 0.33 mm2/s and an exponential rise to a maximum of 18.4 mm2 (r2 = 0.61). This study demonstrated the induction of PCH by LUS of piglets, and supports the safety recommendation for use of MIs <0.4 in neonatal LUS. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma is an aggressive malignancy with limited therapeutic treatments available and a 5-y survival less than 10%. Pancreatic cancers have been found to be immunogenically "cold" with a largely immunosuppressive tumor microenvironment. There is emerging evidence that focused ultrasound can induce changes in the tumor microenvironment and have a constructive impact on the effect of immunotherapy. However, the immune cells and timing involved in these effects remain unclear, which is essential to determining how to combine immunotherapy with ultrasound for treatment of pancreatic adenocarcinoma. We used low-intensity focused ultrasound and microbubbles (LoFU + MBs), which can mechanically disrupt cellular membranes and vascular endothelia, to treat subcutaneous pancreatic tumors in C57BL/6 mice. To evaluate the immune cell landscape and expression and/or localization of damage-associated molecular patterns (DAMPs) as a response to ultrasound, we performed flow cytometry and histology on tumors and draining lymph nodes 2 and 15 d post-treatment. We repeated this study on larger tumors and with multiple treatments to determine whether similar or greater effects could be achieved. Two days after treatment, draining lymph nodes exhibited a significant increase in activated antigen presenting cells, such as macrophages, as well as expansion of CD8+ T cells and CD4+ T cells. LoFU + MB treatment caused localized damage and facilitated the translocation of DAMP signals, as reflected by an increase in the cytoplasmic index for high-mobility-group box 1 (HMGB1) at 2 d. Tumors treated with LoFU + MBs exhibited a significant decrease in growth 15 d after treatment, indicating a tumor response that has the potential for additive effects. Our studies indicate that focused ultrasound treatments can cause tumoral damage and changes in macrophages and T cells 2 d post-treatment. The majority of these effects subsided after 15 d with only a single treatment, illustrating the need for additional treatment types and/or combination with immunotherapy. However, when larger tumors were treated, the effects seen at 2 d were diminished, even with an additional treatment. These results provide a working platform for further rational design of focused ultrasound and immunotherapy combinations in poorly immunogenic cancers. [ABSTRACT FROM AUTHOR]

Purpose: The availability of validated biomarkers to assess radiation exposure and to assist in developing medical countermeasures remains an unmet need.Methods and Materials: We used a cobalt-60 γ-irradiated nonhuman primate (NHP) model to delineate a multiomics-based serum probability index of radiation exposure. Both male and female NHPs were irradiated with different doses ranging from 6.0 to 8.5 Gy, with 0.5 Gy increments between doses. We leveraged high-resolution mass spectrometry for analysis of metabolites, lipids, and proteins at 1, 2, and 6 days postirradiation in NHP serum.Results: A logistic regression model was implemented to develop a 4-analyte panel to stratify irradiated NHPs from unirradiated with high accuracy that was agnostic for all doses of γ-rays tested in the study, up to 6 days after exposure. This panel was comprised of Serpin family A9, acetylcarnitine, glycerophosphocholine (16:0/22:6), and suberylglycine, which showed 2- to 4-fold elevation in serum abundance upon irradiation in NHPs and can potentially be translated as a molecular diagnostic for human use after larger validation studies.Conclusions: Taken together, this study, for the first time, demonstrates the utility of a combinatorial molecular characterization approach using an NHP model for developing minimally invasive assays from small volumes of blood that can be effectively used for radiation exposure assessments. [ABSTRACT FROM AUTHOR]

Loiasis, also called African eye worm, is not currently on WHO's list of priority neglected tropical diseases, even though the risk that individuals with high Loa loa microfilarial densities will develop potentially fatal encephalopathy when they take ivermectin has complicated efforts to use mass drug administration for onchocerciasis (river blindness) and lymphatic filariasis control in co-endemic areas. At least 10 million residents of central and west Africa are thought to have loiasis, which causes painful and itchy subcutaneous oedema, arthralgia, and discomfort when adult helminths that are 3-7 cm in length are present under the conjunctiva of the eye. High levels of microfilaraemia are associated with renal, cardiac, neurological, and other sequelae, and an increased risk of death. The public health burden of loiasis could be greatly reduced with expanded use of diagnostic tests, anthelmintic treatment, and control of the Chrysops spp (tabanid flies) vectors that transmit the parasite. Loiasis should be added to the next revision of the WHO neglected tropical disease priority list, not merely because its inclusion will support the elimination of other skin and subcutaneous neglected tropical diseases, but also because of the complications caused by loiasis itself. [ABSTRACT FROM AUTHOR]

Background: Hydrocephalus is currently managed by cerebrospinal fluid diversion from the cerebral ventricles to other body sites, but this is complicated by obstruction and infection in young infants, thus adding to morbidity and mortality. Studies have reported caffeine to be a pleiotropic neuroprotective drug in the developing brain due to its antioxidant, anti-inflammatory, and antiapoptotic properties, with improved white matter microstructural development. In this study, we investigate the use of caffeine administration as a possible means of pharmacological management for hydrocephalus.Methods: A total of 76 three-day-old mice pups from 10 dams were divided into four groups: hydrocephalus was induced in the pups in two groups by intracisternal injection of kaolin suspension, and their dams were given either caffeine (50 mg/kg by gavage) or water daily for 21 days; the dams in the other 2 (non-hydrocephalic) groups similarly had either caffeine or water; the pups received caffeine administered via lactation. Developmental neurobehavioral tests were performed until day 21, when the pups were sacrificed. Their brains were removed and processed for Cresyl and Golgi staining; both quantitative and qualitative analyses were then carried out.Results: Improved developmental motor activities and reflexes were observed in the hydrocephalus + caffeine-treated pups. Caffeine administration was associated with reduced cell death and increased dendritic arborization of the neurons in the sensorimotor cortex and striatum of hydrocephalic mice pups.Conclusion: Caffeine administration appears to have promise as an adjunct in hydrocephalus management, and its use needs to be further explored. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate renal perfusion changes in rats with acute kidney injury induced by rhabdomyolysis, using quantitative parameters obtained with contrast-enhanced ultrasound (CEUS). Sprague-Dawley (SD) rats were randomly divided into an experimental group (n = 40) and a control group (n = 20). Each group was further divided into four subgroups (0.5-, 6-, 24- and 72-h groups). Time-intensity curves and related quantitative parameters of the renal cortex and medulla were obtained by CEUS, and the contrast characteristics analyzed for different time points. In the experimental group, the CEUS quantitative parameters for the renal medulla of time to peak (TTP), descending time/2 (DT/2) and area under the curve (AUC) increased, whereas ascending slope (AS) and descending slope (DS) decreased. Similarly, renal cortical AS, DS and AUC in the experimental group differed significantly from those in the control group. With respect to the CEUS quantitative parameters for the renal cortex, AUC increased, and AS and DS decreased. These parameters differed significantly between the experimental and control groups. CEUS is sensitive to change in renal perfusion in rhabdomyolysis-induced acute kidney injury and, thus, has diagnostic value. [ABSTRACT FROM AUTHOR]

The aim of the study described here was to investigate the role of viscoelasticity in assessing muscle fibrosis and inflammation in a rat model of contusion using quantitative shear wave elastography (SWE). Unilateral gastrocnemius muscle contusion was induced in 32 male rats using an impactor apparatus. The contralateral muscles served as the control group. SWE was applied to the control group and rats 1, 3, 14 and 21 d after successful modeling (each time point group, n = 8). Histologic features were used as reference standards. The degree of fibrosis was moderately correlated with shear wave speed (r = 0.53), whereas the degree of inflammation was well correlated with shear wave dispersion (SWD) slope (r = 0.74). The area under the receiver operating characteristic curve (AUC) for the dispersion slope for muscle inflammation and fibrosis assessment was 0.87 (95% confidence interval: 0.705-0.963), which exceeded that of the shear wave speed (0.68, 95% confidence interval: 0.494-0.834). The larger decline in dispersion slope in the fibrotic stage than in the inflammation stage (1-d group vs. 14-d group or 21-d group, p < 0.05) indicated better predictive performance than the shear wave speed. [ABSTRACT FROM AUTHOR]

Patients successfully resuscitated from cardiac arrest often have brain injury, myocardial dysfunction, and systemic ischemia-reperfusion injury, collectively termed the post-cardiac arrest syndrome (PCAS). To improve outcomes, potential therapies must be able to be administered early in the post-arrest course and provide broad cytoprotection, as ischemia-reperfusion injury affects all organ systems. Our understanding of the immune system contributions to the PCAS has expanded, with animal models detailing biologically plausible mechanisms of secondary injury, the protective effects of available immunomodulatory drugs, and how immune dysregulation underlies infection susceptibility after arrest. In this narrative review, we discuss the dysregulated immune response in PCAS, human trials of targeted immunomodulation therapies, and future directions for immunomodulation following cardiac arrest. [ABSTRACT FROM AUTHOR]

Background: Survival after out-of-hospital cardiac arrest (OHCA) remains poor. A physiologically distinct cardiopulmonary resuscitation (CPR) strategy consisting of (1) active compression-decompression CPR and/or automated CPR, (2) an impedance threshold device, and (3) automated controlled elevation of the head and thorax (ACE) has been shown to improve neurological survival significantly versus conventional (C) CPR in animal models. This resuscitation device combination, termed ACE-CPR, is now used clinically.Objectives: To assess the probability of OHCA survival to hospital discharge after ACE-CPR versus C-CPR.Methods: As part of a prospective registry study, 227 ACE-CPR OHCA patients were enrolled 04/2019-07/2020 from 6 pre-hospital systems in the United States. Individual C-CPR patient data (n = 5196) were obtained from three large published OHCA randomized controlled trials from high-performing pre-hospital systems. The primary study outcome was survival to hospital discharge. Secondary endpoints included return of spontaneous circulation (ROSC) and favorable neurological survival. Propensity-score matching with a 1:4 ratio was performed to account for imbalances in baseline characteristics.Results: Irrespective of initial rhythm, ACE-CPR (n = 222) was associated with higher adjusted odds ratios (OR) of survival to hospital discharge relative to C-CPR (n = 860), when initiated in <11 min (3.28, 95 % confidence interval [CI], 1.55-6.92) and < 18 min (1.88, 95 % CI, 1.03-3.44) after the emergency call, respectively. Rapid use of ACE-CPR was also associated with higher probabilities of ROSC and favorable neurological survival.Conclusions: Compared with C-CPR controls, rapid initiation of ACE-CPR was associated with a higher likelihood of survival to hospital discharge after OHCA. [ABSTRACT FROM AUTHOR]