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We report a study of the processes of e+e−→K+(D−sD∗0+D∗−sD0) based on e+e− annihilation samples collected with the BESIII detector operating at BEPCII at five center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb−1. An excess over the known contributions of the conventional charmed mesons is observed near the D−sD∗0 and D∗−sD0 mass thresholds in the K+ recoil-mass spectrum for events collected at s√=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5+1.8−2.6±2.1) MeV/c2 and (12.8+5.3−4.4±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 σ over the contributions only from the conventional charmed mesons. This is the first candidate of the charged hidden-charm tetraquark with strangeness, decaying into D−sD∗0 and D∗−sD0. However, the properties of the excess need further exploration with more statistics.
The rare decay 𝜂′→𝜋+𝜋−𝑒+𝑒− is studied using a sample of 1.3×109 𝐽/𝜓 events collected with the BESIII detector at BEPCII in 2009 and 2012. The branching fraction is measured with improved precision to be (2.42±0.05stat±0.08syst)×10−3. Due to the inclusion of new data, this result supersedes the last BESIII result on this branching fraction. In addition, the 𝐶𝑃-violating asymmetry in the angle between the decay planes of the 𝜋+𝜋−-pair and the 𝑒+𝑒−-pair is investigated. A measurable value would indicate physics beyond the standard model; the result is 𝒜𝐶𝑃=(2.9±3.7stat±1.1syst)%, which is consistent with the standard model expectation of no 𝐶𝑃-violation. The precision is comparable to the asymmetry measurement in the 𝐾0𝐿→𝜋+𝜋−𝑒+𝑒− decay where the observed (14±2)% effect is driven by a standard model mechanism.
Search for the reaction channel e⁺e⁻ → ηcηπ⁺π⁻ at center-of-mass energies from 4.23 to 4.60 GeV
(2021)
Using data collected with the BESIII detector operating at the Beijing Electron Positron Collider, we search for the process 𝑒+𝑒−→𝜂𝑐𝜂𝜋+𝜋−. The search is performed using five large datasets recorded at center-of-mass energies of 4.23, 4.26, 4.36, 4.42, and 4.60 GeV. The 𝜂𝑐 meson is reconstructed in 16 exclusive decay modes. No signal is observed in the 𝜂𝑐 mass region at any center-of-mass energy. The upper limits on the reaction cross sections are determined to be 6.2, 10.8, 27.6, 22.6 and 23.7 pb at the 90% confidence level at the center-of-mass energies listed above.
Background: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of MYCN oncogene amplification (MNA). Methods: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group). Results: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39–54%) and 56% (95%-CI 49–63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18–31%, p < 0.001; OS 32% 95%-CI 25–39%, p < 0.001). The presence of RAS-/p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively; both p < 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS (p < 0.001 and p = 0.011, respectively). Conclusions: Neuroblastoma patients attributed to high risk solely by MYCN amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.
Structured RNA regions are important gene control elements in prokaryotes and eukaryotes. Here, we show that the mRNA of a cyanobacterial heat shock gene contains a built-in thermosensor critical for photosynthetic activity under stress conditions. The exceptionally short 5´-untranslated region is comprised of a single hairpin with an internal asymmetric loop. It inhibits translation of the Synechocystis hsp17 transcript at normal growth conditions, permits translation initiation under stress conditions and shuts down Hsp17 production in the recovery phase. Point mutations that stabilized or destabilized the RNA structure deregulated reporter gene expression in vivo and ribosome binding in vitro. Introduction of such point mutations into the Synechocystis genome produced severe phenotypic defects. Reversible formation of the open and closed structure was beneficial for viability, integrity of the photosystem and oxygen evolution. Continuous production of Hsp17 was detrimental when the stress declined indicating that shutting-off heat shock protein production is an important, previously unrecognized function of RNA thermometers. We discovered a simple biosensor that strictly adjusts the cellular level of a molecular chaperone to the physiological need.
Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma
(2016)
Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics.
Background: Extremity fracture is frequently seen in multiple traumatized patients. Local post-traumatic inflammatory reactions as well as local and systemic interactions have been described in previous studies. However, trauma severity and its impact on the local immunologic reaction remains unclear. Therefore, fracture-associated local inflammation was investigated in a porcine model of isolated and combined trauma to gain information about the early inflammatory stages.
Material and Methods: Polytrauma (PT) consisted of lung contusion, liver laceration, femur fracture, and controlled hemorrhage. Monotrauma (MT) consisted of femur fracture only. The fracture was operatively stabilized and animals were monitored under ICU-standard for 72 h. Blood, fracture hematoma (FH) as well as muscle samples were collected throughout the experimental period. Levels of local and systemic pro- and anti-inflammatory as well as angiogenetic cytokines were measured by ELISA.
Results: Both groups showed a significant decrease in pro-inflammatory IL-6 in FH over time. However, concentrations in MT were significantly higher than in PT. The IL-8 concentrations initially decreased in FH, but recovered by the end of the observation period. These dynamics were only statistically significant in MT. Furthermore, concentrations measured in muscle tissue showed inverse kinetics compared to those in FH. The IL-10 did not present statistical resilient dynamics over time, although a slight increase in FH was seen by the end of the observation time in the MT group.
Conclusions: Time-dependent dynamics of the local inflammatory response were observed. Trauma severity showed a significant impact, with lower values in pro- as well as angiogenetic mediators. Fracture repair could be altered by these trauma-related changes of the local immunologic milieu, which might serve as a possible explanation for the higher rates of delayed or non-union bone repair in polytraumatised patients.
Aims: The ILUVIEN Registry Safety Study is an ongoing, multicentre, open-label, observational study collecting real-world data on the safety and effectiveness of the 0.2 µg/day fluocinolone acetonide (FAc) implant in patients treated according to the European label requirements.
Methods: Patients included in this analysis were treated for the licensed indication of chronic diabetic macular oedema (cDMO; that is, DMO that persists or recurs despite treatment). Data presented in the current analysis were collected from patient records up to 6 March 2017. Visual acuity (VA) data, including mean change in VA over time and at last observation, intraocular pressure (IOP) over the course of the study, IOP events, use of IOP-lowering therapy and cup:disc ratio were analysed. Information on additional DMO treatments post-FAc implant was also captured.
Results: Five hundred and sixty-three patients (593 eyes) were enrolled on the study. Mean IOP for the overall population remained within the normal range throughout follow-up and 76.7% of patients did not require IOP-lowering therapy following treatment with the FAc implant. Sixty-nine per cent of eyes did not require additional DMO treatments. Mean VA in the overall population increased from 51.9 letters at baseline to 55.6 letters at month 12, with a significant increase of 2.9 letters at last observation. Patients with short-term cDMO experienced greater VA gains than those with long-term cDMO.
Conclusions: The results of this analysis are comparable with those of other studies, including the Fluocinolone Acetate for Macular Edema study. The study reinforces the good safety and effectiveness profile of FAc, and demonstrates the benefit of early FAc treatment.
Background: Severely injured patients experience substantial immunological stress in the aftermath of traumatic insult, which often results in systemic immune dysregulation. Regulatory T cells (Treg) play a key role in the suppression of the immune response and in the maintenance of immunological homeostasis. Little is known about their presence and dynamics in blood after trauma, and nothing is known about Treg in the porcine polytrauma model. Here, we assessed different subsets of Treg in trauma patients (TP) and compared those to either healthy volunteers (HV) or data from porcine polytrauma.
Methods: Peripheral blood was withdrawn from 20 TP with injury severity score (ISS) ≥16 at the admittance to the emergency department (ED), and subsequently on day 1 and at day 3. Ten HV were included as controls (ctrl). The porcine polytrauma model consisted of a femur fracture, liver laceration, lung contusion, and hemorrhagic shock resulting in an ISS of 27. After polytrauma, the animals underwent resuscitation and surgical fracture fixation. Blood samples were withdrawn before and immediately after trauma, 24 and 72 h later. Different subsets of Treg, CD4+CD25+, CD4+CD25+FoxP3+, CD4+CD25+CD127−, and CD4+CD25+CD127−FoxP3+ were characterized by flow cytometry.
Results: Absolute cell counts of leukocytes were significantly increasing after trauma, and again decreasing in the follow-up in human and porcine samples. The proportion of human Treg in the peripheral blood of TP admitted to the ED was lower when compared to HV. Their numbers did not recover until 72 h after trauma. Comparable data were found for all subsets. The situation in the porcine trauma model was comparable with the clinical data. In porcine peripheral blood before trauma, we could identify Treg with the typical immunophenotype (CD4+CD25+CD127−), which were virtually absent immediately after trauma. Similar to the human situation, most of these cells expressed FoxP3, as assessed by intracellular FACS stain.
Conclusion: Despite minor percental differences in the recovery of Treg populations after trauma, our findings show a comparable decrease of Treg early after polytrauma, and strengthen the immunological significance of the porcine polytrauma model. Furthermore, the Treg subpopulation CD4+CD25+CD127− was characterized in porcine samples.
Background: Surgical complications are associated with a significant burden to patients and hospitals and are increasingly discussed in recent literature. This cohort study reviewed surgery-related complications in a Level I trauma center. The effect of a complication avoidance care bundle on the rate of surgical complications was analyzed. Methods: All complications (surgical and nonsurgical) that occur in our trauma department are prospectively captured using a standardized documentation form and are discussed and analyzed in a weekly trauma Morbidity and Mortality (M&M) conference. Surgical complication rates are calculated using the annual surgical procedure numbers. Based on discussions in the M&M conference, a complication avoidance care bundle consisting of five measures was established: (1) Improving team situational awareness; (2) reducing operating room traffic by staff members and limiting door-opening events; (3) preoperative screening for infectious foci; (4) adapted preoperative antibiotic prophylaxis in anatomic regions with a high risk of infectious complications; and (5) use of iodine-impregnated adhesive drape. Results: The number of surgical procedures steadily increased over the study years, from 3587 in 2015 to 3962 in 2019 (an increase of 10.5%). Within this 5-year study period, the overall rate of surgical complications was 0.8%. Surgical site infections were the most frequently found complications (n = 40, 24.8% of all surgical complications), followed by screw malposition (n = 20, 12.4%), postoperative dislocations of arthroplasties (n = 18, 11.2%), and suboptimal fracture reduction (n = 18, 11.2%). Following implementation of the complication avoidance care bundle, the overall rate of surgical complications significantly decreased, from 1.14% in the year 2016 to 0.56% in the study year 2019, which represents a reduction of 51% within a 3-year time period. Conclusions: A multimodal strategy targeted at reducing the surgical complication rate can be successfully established based on a transparent discussion of adverse surgical outcomes. The combination of the different preventive measures was associated with reducing the overall complication rate by half within a 3-year time period.