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Data from: Inhibition of Smurf2 translation by miR-322/503 protects from ischemia reperfusion injury by modulating EZH2/Akt/GSK3β signaling
BACKGROUND: myocardial ischemia/reperfusion (I/R) is a common and lethal disease that threatens people's life worldwide. The underlying mechanisms are under intensive study and yet remain unclear. Here, we explored the function of miR-322/503 in myocardial I/R injury. METHODS: We used isolated rat perfused heart as an in vivo model and H9c2 cells subjected with the oxygen and glucose deprivation followed by reperfusion (OGD/R) as in vitro model to study myocardial I/R injury. TTC staining was used to measure the infarct size and TUNEL staining was used to examine apoptosis. qRT-PCR and western blot were used to determine expression levels of miR-322/503, Smurf2, EZH2, p-Akt, p-GSK3β. RESULTS: Overexpression of miR-322/503 decreased infarct size, inhibited cell apoptosis and promoted cell proliferation through up-regulation of p-Akt and p-GSK3β. Thus, the expression of miR-322/503 was reduced during I/R process. On the molecular level, miR-322/503 directly bound Smurf2 mRNA and suppressed its translation. Smurf2 ubiquitinated EZH2 and degraded EZH2 which could activate Akt/GSK3β signaling. CONCLUSIONS: Our study demonstrates that miR-322/503 plays a beneficial role in myocardial I/R injury. By inhibition of Smurf2 translation, miR-322/503 induces EZH2 expression and activates Akt/GSK3β pathway, thereby protecting cells from ischemia reperfusion injury.
Data from: Implementation of new standard operating procedures for geriatric trauma patients with multiple injuries: a single level I trauma centre study
<p class="Abstract"><b>Background</b></p> <p class="Abstract">The demographic changes towards ageing of the populations in developed countries impose a challenge to trauma centres, as geriatric trauma patients require specific diagnostic and therapeutic procedures. This study investigated whether the integration of new standard operating procedures (SOPs) for the resuscitation room (ER) has an impact on the clinical course in geriatric patients. The new SOPs were designed for severely injured adult trauma patients, based on the Advanced Trauma Life Support (ATLS) and imply early whole-body computed tomography (CT), damage control surgery, and the use of goal-directed coagulation management.</p> <p class="Abstract"><b>Methods</b></p> <p class="Abstract">Single-centre cohort study. We included all patients ≥ 65 years of age with an Injury Severity Score (ISS) ≥ 9 who were admitted to our hospital primarily via ER. A historic cohort was compared to a cohort after the implementation of the new SOPs.</p> <p class="Abstract"><b>Results</b></p> <p class="Abstract">We enrolled 311 patients who met the inclusion criteria between 2000–2006 (group <i>Pre</i>SOP) and 2010–2012 (group SOP). There was a significant reduction in the mortality rate after the implementation of the new SOPs (<i>P</i> = .001). This benefit was seen only for severely injured patients (ISS ≥ 16), but not for moderately injured patients (ISS 9–15). There were no differences with regard to infection rates or rate of palliative care.</p> <p class="Abstract"><b>Conclusions</b></p> <p class="Abstract">We found an association between implementation of new ER SOPs, and a lower mortality rate in severely injured geriatric trauma patients, whereas moderately injured patients did not obtain the same benefit.</p>
Data from: Can microstructural MRI detect subclinical tissue injury in subjects with asymptomatic cervical spinal cord compression? a prospective cohort study
Objectives: Degenerative cervical myelopathy (DCM) involves extrinsic spinal cord compression causing tissue injury and neurological dysfunction. Asymptomatic spinal cord compression (ASCC) is more common but its significance is poorly defined. This study investigates if: 1) ASCC can be automatically diagnosed using spinal cord shape analysis; 2) multiparametric quantitative MRI can detect similar spinal cord tissue injury as previously observed in DCM. Design: Prospective observational longitudinal cohort study. Setting: Single centre, tertiary care and research institution. Participants: 40 neurologically intact subjects (19 female, 21 male) divided into groups with and without ASCC. Interventions: None. Outcome Measures: Clinical assessments: modified Japanese Orthopedic Association (mJOA) score and physical examination. 3T MRI assessments: automated morphometric analysis compared with consensus ratings of spinal cord compression, and measures of tissue injury: cross-sectional area (CSA), diffusion fractional anisotropy (FA), magnetization transfer ratio (MTR), and T2-weighted imaging white to grey matter signal intensity ratio (T2WI WM/GM) extracted from rostral (C1-3), caudal (C6-7), and maximally compressed levels (MCL). Results: ASCC was present in 20/40 subjects. Diagnosis with automated shape analysis showed area under the curve > 97%. Five MRI metrics showed differences suggestive of tissue injury in ASCC compared with uncompressed subjects (p<0.05), while a composite of all 10 measures (average of z scores) showed highly significant differences (p=0.002). At follow-up (median 21 months), two ASCC subjects developed DCM. Conclusions: ASCC appears to be common and can be accurately and objectively diagnosed with automated morphometric analysis. Quantitative MRI appears to detect subclinical tissue injury in ASCC prior to the onset of neurological symptoms and signs. These findings require further validation, but offer the intriguing possibility of pre-symptomatic diagnosis and treatment of DCM and other spinal pathologies. Registration: Not registered.
Supplemental Data for Cerebral Oxygen Metabolic Stress, Microstructural Injury, and Infarction in Adults With Sickle Cell Disease
<p>Supplemental data to manuscript</p>
Data from: Characteristics of patients included and enrolled in studies on the prognostic value of serum biomarkers for prediction of post-concussion symptoms following a mild traumatic brain injury: a systematic review
Objective: Mild traumatic brain injury (mTBI) has been insufficiently researched and its definition remains elusive. Investigators are confronted by heterogeneity in patients, mechanism of injury and outcomes. Findings are thus often limited in generalizability and clinical application. Serum protein biomarkers are increasingly assessed to enhance prognostication of outcomes but their translation into clinical practice has yet to be achieved. A systematic review was performed to describe the adult populations included and enrolled in studies that evaluated the prognostic value of protein biomarkers to predict post-concussion symptoms following a mTBI. Data sources: Searches of MEDLINE, EMBASE, CENTRAL, CINAHL, Web of Science, PsycBITE, and PsycINFO up to October 2016. Data selection and extraction: Two reviewers independently screened for potentially eligible studies, extracted data and assessed the overall quality of evidence by outcome using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: A total of 23,298 citations were obtained from which 166 manuscripts were reviewed. Thirty-six cohort studies (2,812 patients) having enrolled between 7 and 311 patients (median 89) fulfilled our inclusion criteria. Most studies excluded patients based on advanced age (n=10 (28%)), neurologic disorders (n=20 (56%)), psychiatric disorders (n=17 (47%)), substance abuse disorders (n=13 (36%)) or previous TBI (n=10 (28%)). Twenty-one studies (58%) used at least two of these exclusion criteria. The pooled mean age of included patients was 39.3 (SD 4.6) years old (34 studies). The criteria used to define a mTBI were inconsistent. The most frequently reported outcome was post-concussion syndrome (PCS) using the Rivermead Post-Concussion Symptoms Questionnaire (n=18 (50%)) with follow-ups ranging from 7 days to 5 years after the mTBI. Conclusions: Most studies have recruited samples that are not representative and generalizable to the mTBI population. These exclusion criteria limit the potential use and translation of promising serum protein biomarkers to predict post-concussion symptoms.
Data from: Perceptions of football players regarding injury risk factors and prevention strategies
Current approaches regarding injury prevention focus on the transfer of evidence into daily practice. One promising approach is to influence attitudes and beliefs of players. The objective of this study was to record player's perceptions on injury prevention. A survey was performed among players of one German high-level football (soccer) club. 139 professional and youth players between age 13 and 35 years completed a standardized questionnaire (response rate = 98%). It included categories with (1) history of lower extremity injuries, (2) perceptions regarding risk factors and (3) regularly used prevention strategies. The majority of players (84.2%) had a previous injury. 47.5% of respondents believe that contact with other players is a risk factor, followed by fatigue (38.1%) and environmental factors (25.9%). The relevance of previous injuries as a risk factor is differently perceived between injured (25%) and uninjured players (0.0%). Nearly all players (91.5%) perform stretching to prevent injuries, followed by neuromuscular warm up exercises (54.0%). Taping is used by 40.2% of previously injured players and 13.6% of players without a history of injuries. In conclusion, the perception of risk factors and performed preventive strategies are inconsistent with scientific evidence. Future transfer strategies should incorporate the players believes and attitudes.
Data from: Transcriptomic response to injury sheds light on the physiological costs of reproduction in ant queens
The trade-off between reproduction and longevity is widespread among multicellular organisms. As an important exception, the reproductive females of perennial social insects (ants, honeybees, termites) are simultaneously highly fertile and very long-lived relative to their nonreproductive nestmates. The observation that increased fecundity is not coupled with decreased lifespan suggests that social insect queens do not have to reallocate resources between reproduction and self-maintenance. If queens have to compensate for the costs of reproduction on the level of the individual, the activation of other energy-demanding physiological processes might force them to reduce the production of eggs. To test this hypothesis in ant queens, we increased immunity costs by injury and measured the effect of this treatment on egg-laying rates and genomewide gene expression. Amputation of both middle legs led to a temporary decrease in egg-laying rates and affected the expression of 947 genes corresponding to 9% of the transcriptome. The changes comprised the upregulation of the immune and wound healing response on the one hand, and the downregulation of germ cell development, central nervous system development and learning ability on the other hand. Injury strongly influenced metabolism by inducing catabolism and repressing amino acid and nitrogen compound metabolism. By comparing our results to similar transcriptomic studies in insects, we found a highly consistent upregulation of immune genes due to sterile and septic wounding. The gene expression changes, complemented by the temporary decline of egg-laying rates, clearly reveal a trade-off between reproduction and the immune response in social insect queens.
Data from: Use of anisotropy, 3D segmented atlas, and computational analysis to identify gray matter subcortical lesions common to concussive injury from different sites on the cortex
Traumatic brain injury (TBI) can occur anywhere along the cortical mantel. While the cortical contusions may be random and disparate in their locations, the clinical outcomes are often similar and difficult to explain. Thus a question that arises is, do concussions at different sites on the cortex affect similar subcortical brain regions? To address this question we used a fluid percussion model to concuss the right caudal or rostral cortices in rats. Five days later, diffusion tensor MRI data were acquired for indices of anisotropy (IA) for use in a novel method of analysis to detect changes in gray matter microarchitecture. IA values from over 20,000 voxels were registered into a 3D segmented, annotated rat atlas covering 150 brain areas. Comparisons between left and right hemispheres revealed a small population of subcortical sites with altered IA values. Rostral and caudal concussions were of striking similarity in the impacted subcortical locations, particularly the central nucleus of the amygdala, laterodorsal thalamus, and hippocampal complex. Subsequent immunohistochemical analysis of these sites showed significant neuroinflammation. This study presents three significant findings that advance our understanding and evaluation of TBI: 1) the introduction of a new method to identify highly localized disturbances in discrete gray matter, subcortical brain nuclei without postmortem histology, 2) the use of this method to demonstrate that separate injuries to the rostral and caudal cortex produce the same subcortical, disturbances, and 3) the central nucleus of the amygdala, critical in the regulation of emotion, is vulnerable to concussion.
Data from: A randomised trial comparing the clinical effectiveness of different emergency department healthcare professionals in soft tissue injury management
OBJECTIVE: To evaluate the clinical effectiveness of soft tissue injury management by emergency nurse practitioners (ENPs) and extended scope physiotherapists (ESPs) compared to the routine care provided by doctors in a UK emergency department (ED). DESIGN: Randomised, pragmatic trial of equivalence. SETTING: One adult ED in England. PARTICIPANTS: 372 patients were randomised; 126 to the ESP group, 123 to the ENP group and 123 to the doctor group. Participants were adults (older than 16 years) presenting to the ED with a peripheral soft tissue injury eligible for management by any of the three professional groups. Patients were excluded if they had any of the following: injury greater than 72 hours old; systemic disease; dislocated joints; recent surgery; unable to give informed consent (eg, dementia), open wounds; major deformities; opiate analgesia required; concurrent chest/rib injury; neurovascular deficits and associated fracture. INTERVENTIONS: Patients were randomised to treatment by ESPs, ENPs or routine care provided by doctors (of all grades). MAIN OUTCOME MEASURES: Upper-limb and lower-limb functional scores, quality of life, physical well-being, preference-based health measures and the number of days off work. RESULTS: The clinical outcomes of soft tissue injury treated by ESPs and ENPs in the ED were equivalent to routine care provided by doctors. CONCLUSIONS: As all groups were clinically equivalent it is other factors such as cost, workforce sustainability, service provision and skill mix that become important. This result validates the role of the ENP, which is becoming established as an integral part of minor injuries care, and demonstrates that the ESP should be considered as part of the clinical skill mix without detriment to outcomes. ISRCTN-ISRCTN trials register number 70891354.
Data from: Optimizing mouse surgery with online rectal temperature monitoring and preoperative heat supply. Effects on post-ischemic acute kidney injury.
Body temperature affects outcomes of tissue injury. We hypothesized that online body core temperature recording and selective interventions help to standardize peri-interventional temperature control and the reliability of outcomes in experimental renal ischemia reperfusion injury (IRI). We recorded core temperature in up to seven mice in parallel using a Thermes USB recorder and ret-3-iso rectal probes with three different protocols. Setup A: Heating pad during ischemia time; Setup B: Heating pad from incision to wound closure; Setup C: A ventilated heating chamber before surgery and during ischemia time with surgeries performed on a heating pad. Temperature profile recording displayed significant declines upon installing anesthesia. The profile of the baseline experimental setup A revealed that <1 % of the temperature readings were within the target range of 36.5 to 38.5 °C. Setup B and C increased the target range readings to 34.6 ± 28.0 % and 99.3 ± 1.5 %, respectively. Setup C significantly increased S3 tubular necrosis, neutrophil influx, and mRNA expression of kidney injury markers. In addition, using setup C different ischemia times generated a linear correlation with acute tubular necrosis parameters at a low variability, which further correlated with the degree of kidney atrophy 5 weeks after surgery. Changing temperature control setup A to C was equivalent to 10 minutes more ischemia time. We conclude that body temperature drops quickly in mice upon initiating anesthesia. Immediate heat supply, e.g. in a ventilated heating chamber, and online core temperature monitoring can help to standardize and optimize experimental outcomes.
Data from: Candidate risk factors and mechanisms for tolvaptan-induced liver injury are identified using a collaborative cross approach
Clinical trials of tolvaptan showed it to be a promising candidate for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) but also revealed potential for idiosyncratic drug-induced liver injury (DILI) in this patient population. To identify risk factors and mechanisms underlying tolvaptan DILI, 8 mice in each of 45 strains of the genetically diverse Collaborative Cross (CC) mouse population were treated with a single oral dose of either tolvaptan or vehicle. Significant elevations in plasma alanine aminotransferase (ALT) were observed in tolvaptan-treated animals in 3 of the 45 strains. Genetic mapping coupled with transcriptomic analysis in the liver was used to identify several candidate susceptibility genes including epoxide hydrolase 2, interferon regulatory factor 3, and mitochondrial fission factor. Gene pathway analysis revealed that oxidative stress and immune response pathways were activated in response to tolvaptan treatment across all strains, but genes involved in regulation of bile acid homeostasis were most associated with tolvaptan-induced elevations in ALT. Secretory leukocyte peptidase inhibitor (Slpi) mRNA was also induced in the susceptible strains and was associated with increased plasma levels of Slpi protein, suggesting a potential serum marker for DILI susceptibility. In summary, tolvaptan induced signs of oxidative stress, mitochondrial dysfunction, and innate immune response in all strains, but variation in bile acid homeostasis was most associated with susceptibility to the liver response. This CC study has indicated potential mechanisms underlying tolvaptan DILI and biomarkers of susceptibility that may be useful in managing the risk of DILI in ADPKD patients.
FIGURE 10 in A study of some species of the genus Stictococcus Cockerell (Hemiptera: Sternorrhyncha: Coccoidea: Stictococcidae), and a discussion on Stictococcus vayssierei Richard, a species injurious to cassava in Equatorial Africa with a description of a new species from Nigeria
FIGURE 10. Stictococcus vayssierei Richard, adult female.
FIGURE 8 in A study of some species of the genus Stictococcus Cockerell (Hemiptera: Sternorrhyncha: Coccoidea: Stictococcidae), and a discussion on Stictococcus vayssierei Richard, a species injurious to cassava in Equatorial Africa with a description of a new species from Nigeria
FIGURE 8. Stictococcus sjostedti Cockerell & Cockerell, adult female.
FIGURE 7 in A study of some species of the genus Stictococcus Cockerell (Hemiptera: Sternorrhyncha: Coccoidea: Stictococcidae), and a discussion on Stictococcus vayssierei Richard, a species injurious to cassava in Equatorial Africa with a description of a new species from Nigeria
FIGURE 7. Stictococcus pujoli Richard, adult female.
FIGURE 5 in A study of some species of the genus Stictococcus Cockerell (Hemiptera: Sternorrhyncha: Coccoidea: Stictococcidae), and a discussion on Stictococcus vayssierei Richard, a species injurious to cassava in Equatorial Africa with a description of a new species from Nigeria
FIGURE 5. Stictococcus formicarius Newstead, adult female.
FIGURE 1 in A study of some species of the genus Stictococcus Cockerell (Hemiptera: Sternorrhyncha: Coccoidea: Stictococcidae), and a discussion on Stictococcus vayssierei Richard, a species injurious to cassava in Equatorial Africa with a description of a new species from Nigeria
FIGURE 1. Outline Map of Africa showing distribution of the family Stictococcidae.
FIGURE 6 in A study of some species of the genus Stictococcus Cockerell (Hemiptera: Sternorrhyncha: Coccoidea: Stictococcidae), and a discussion on Stictococcus vayssierei Richard, a species injurious to cassava in Equatorial Africa with a description of a new species from Nigeria
FIGURE 6. Stictococcus intermedius Newstead, adult female.
FIGURE 4 in A study of some species of the genus Stictococcus Cockerell (Hemiptera: Sternorrhyncha: Coccoidea: Stictococcidae), and a discussion on Stictococcus vayssierei Richard, a species injurious to cassava in Equatorial Africa with a description of a new species from Nigeria
FIGURE 4. Body segmentation of adult female of Stictococcus.
FIGURE 9 in A study of some species of the genus Stictococcus Cockerell (Hemiptera: Sternorrhyncha: Coccoidea: Stictococcidae), and a discussion on Stictococcus vayssierei Richard, a species injurious to cassava in Equatorial Africa with a description of a new species from Nigeria
FIGURE 9. Stictococcus subterreus Williams, Matile-Ferrero & Miller sp. n., adult female.
EV71 induced skeletal muscle injury in BALB/c lactating mice through the Caspase-1/IL-1β signaling pathway
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