Abstract
The CERN Linear Electron Accelerator for Research (CLEAR) has been operating as a user facility since 2017, providing beams for various experiments. This paper describes a start-to-end ...optimisation of the CLEAR beamline as a driver for X-ray generation through inverse Compton scattering. The novel particle tracking code RF-Track was used to simulate the electron beam from the bunch generation at the cathode up to the interaction with a laser beam. Figures of merit of the scattered photon beam were computed in RF-Track, and optimised by tuning the beam parameters at injection and quadrupole strengths across the beamline. The aim of the optimisation was to maximise the scattered photon flux, and minimise the effects from static and dynamic imperfections. The start-to-end model of the CLEAR beamline was used to derive the impact of jitter on flux.
T-cell immunoglobulin and mucin domain 3 (TIM3) is emerging as a potential target for antibody-based checkpoint blockade. However, the efficacy of TIM3 blockade in combination with other treatment ...modalities, has not been extensively studied. In the current work we combined TIM3 blockade with myxoma virus-based oncolytic virotherapy (OV). Our results demonstrate that myxoma virus's ability to initiate an immense antitumor immune response complements the ability of TIM3 blockade to shift the tumor microenvironment to a more proinflammatory state. As a result, the combination of TIM3 blockade and OV is able to completely eradicate established disease, while neither monotherapy is effective. These data represent the first demonstration that OV can enhance the efficacy of TIM3 blockade and suggest that this treatment may need to be incorporated into more aggressive, combinatorial regimens in order to fulfill its potential as an immunotherapeutic.
Type 2 Diabetes Mellitus is a leading cause of end stage renal disease in the worldwide. Inflammation is regarded as one of the main reasons for the progression of diabetes complications. We aimed to ...evaluate the association of neutrophil to lymphocyte ratio (NLR) as indicator of systemic inflammation with diabetic retinopathy and nephropathy.
This is a cross-sectional study of 114 prevalent type 2 diabetic subjects. All of the patients underwent detailed examination for the presence of diabetic retinopathy and nephropathy. Diabetic retinopathy was approved and classified according to findings based on flouresceint fundal angiography results. Estimated glomerular filtration rate (eGFR) and microalbumin to creatinine ratio were calculated to establish the diabetic nephropathy. NLR was calculated as ratio of absolute neutrophil count to absolute lymphocyte count.
Retinopathy was present in 55 (48.2%) out of 114 patients, whereas nephropathy was present in 62 patients (54.3%). NLR was significantly higher in patients with nephropathy than in patients without nephropathy. NLR was also positively correlated with CRP (p=0.017, r=0.224) and microalbuminuria (p=0.016, r=0.257) whereas negatively correlated with eGFR (p<0.001, r=-0.337) values in the whole cohort. NLR was independent predictors for diabetic nephropathy, whereas it did not appear as an independent associate of diabetic retinopathy.
NLR and diabetic nephropathy have an independent association between them whereas there was no independent association between NLR with retinopathy in type 2 diabetic patients.
Highlights • Synaptic plasticity at the perforant path (pp)-CA1 synapses in vivo was studied. • LTP at this synapse is only partially dependent on NMDA receptors. • Blockade of NMDAR and ...voltage-gated calcium channels fully prevents LTP. • Agonism of group II mGlu receptors depresses synaptic transmission but not LTP. • The neurotransmitter receptor-regulation of this synapse is completely distinct.
Children who underwent hematopoietic stem cell transplant (HSCT) transplants are at high risk of developing central-line-associated bloodstream infections (CLABSIs). The present study aimed to ...identify possible risk factors for mortality by analyzing the clinical and laboratory characteristics of patients diagnosed with CLABSI in our pediatric hematopoietic stem cell transplant unit.
The initial CLABSI episodes of 102 children were analyzed. Medical records of the patients were evaluated by preformed standardized surveys. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors for mortality.
Thirty-five patients (34.3%) were female. The median age was 48 months (3-204). The median time to onset of CLABSI was 19 days (4-150). The gram-negative and gram-positive bacteria ratio among the causative agents was 57.8% to 34.3%. The mortality rate was 12.6%. The presence of severe neutropenia, initiation of inappropriate empirical antibiotic therapy, the presence of hypotension, persistent bacteremia, pediatric intensive care unit admission, growth of carbapenemase-positive gram-negative microorganism and multidrug-resistant bacteria were significantly high in the mortality group when compared to survivors. The presence of hypotension, inappropriate empirical antibiotic therapy, and persistent bacteremia were found to be independent risk factors for mortality.
Rational use of antibiotics, active surveillance and screening of patients together with improved infection control practices may reduce the incidence and the consequences of CLABSIs.
Glioblastoma (GBM) is the most prevalent and deadliest subtype of glioma. Despite current innovations in existing therapeutic modalities, GBM remains incurable, and alternative therapies are ...required. Previously, we demonstrated that Olea europaea leaf extract (OLE) kills GBM cells by modulating miR-181b, miR-137, miR-153 and Let-7d expression. However, although oleuropein (OL) is the main compound in OLE, its role in the antitumour effect of OLE remains unknown. This study determined the effect of OL on GBM cell line T98G and compared the results with our previous findings regarding the effect of OLE on the same cell line. The antiproliferative activity of OL and its effect on temozolomide (TMZ) response were tested inT98G cells using WST-1 assay. OL inhibition was evaluated using one-way analysis of variance with Tukey’s post hoc test. The effect of OL on miR-181b, miR-137, miR-153 and Let-7d expression was assessed using quantitative reverse transcription polymerase chain reaction. Fold differences in expression between untreated, OL or OL + TMZ-treated samples were calculated using 2−ΔCt method. Significance was evaluated using an independent sample t-test. Treatment with 277.5 and 555 µM OL resulted in 39.51% and 75.40% reductions in T98G cells within 24 h. Coadministration of 325 µM TMZ and 277.5 or 555 µM, OL caused 2.08- and 2.83-fold increases, respectively, in the therapeutic effect of TMZ. OL + TMZ significantly increased microRNA expression, particularly Let-7d, than OLE. In conclusion, OL has an antitumour effect on GBM cells mainly via regulation of Let-7d expression. The present results also indicate other minor compounds in OLE play important anticancer roles.
•Candida parapsilosis was the most frequent causative agent in patients with candidemia.•Dialysis and concurrent bacteremia are strong predictors of mortality within 30 days in patients with ...candidemia.•Follow-up blood cultures have a protective role with lower mortality rates within 30 days in patients with candidemia.
The aim of this study was to evaluate the possible risk factors for mortality in adult patients with candidemia by investigating the causative agents, underlying conditions and predisposing factors.
The data including causative Candida species, predisposing factors, and underlying conditions of candidemia patients between the years 2015–2017 were collected and the impact of these factors on mortality was evaluated. Patients were divided into two groups as died (died patients within 30 days of the onset of candidemia) and survived and risk factors were evaluated for each group.
We found 163 adult candidemia cases during the study period. Overall 30-day mortality was 40.5%. Candida parapsilosis was the most frequent causative agent (49.1%). C. parapsilosis candidemia was more common in the survived group compared with the died group (n: 49 (61.3%) vs. n: 31 (38.8%), P=0.888). Mortality rates were significantly higher in patients with dialysis (n: 27 (69.2%) vs. n: 12 (30.8%), P<0.00) and concurrent bacteremia (n: 20 (57.1%) vs. n: 15 (42.9%), P=0.024). Survival rates were significantly higher in patients with follow-up blood cultures (n: 75 (65.8%) vs. n: 39 (34.2%), P=0.013). The most important source of candidemia was catheter (49.7%), and C. parapsilosis was the most common causative agent (58%). The catheter was removed in 96.3% of these patients and the mortality rate was 38.5%. All of the patients received antifungal therapy and there was no significant difference between the effects of antifungals on mortality (n: 65 (39.9%) vs. 98 (60.1%), P=0.607).
Dialysis and concurrent bacteremia are strong predictors of mortality in 30 days within patients with candidemia, whereas follow-up blood cultures have a protective role with lower mortality rates. In our study, the most important source of candidemia was catheter, and C. parapsilosis was the most common causative agent. The catheter was removed in almost all patients and the mortality rate was almost one third among these patients.
Aim
To investigate the changes in the biomarker levels related to inflammation and tissue destruction in the periapical exudate of mandibular pre‐molar teeth with asymptomatic apical periodontitis ...after receiving intracanal cryotherapy, to compare cryotherapy and control groups in terms of analgesic intake, interappointment, and post‐operative pain and evaluate the correlation between biomarker levels and interappointment pain.
Methodology
Mandibular pre‐molar teeth of 44 patients aged 18–35 years, diagnosed with asymptomatic apical periodontitis, were root canal treated in two visits (registered as NCT04798144). Baseline periapical exudate samples were obtained, and the patients were assigned to either control or intracanal cryotherapy group according to the final irrigation with distilled water either at room temperature or 2.5°C. The canals were dressed with calcium hydroxide. In the second visit, the calcium hydroxide was removed with passive ultrasonic irrigation, and the periapical exudate was sampled again. IL‐1β, IL‐2, IL‐6, IL‐8, TNF‐α, PGE2 and MMP‐8 levels were determined with ELISA. Post‐operative pain levels were recorded for 6 days following both visits using a visual analogue scale. Data were analysed using t‐test, the Mann–Whitney U test and correlation tests.
Results
There was a significant correlation between the pain scores reported after first visit and IL‐1β and PGE2 levels (p < .05). IL‐1β, IL‐2 and IL‐6 levels showed no significant difference in the cryotherapy group (p > .05), while they significantly increased in the control group (p < .05). There was a decrease in IL‐8, TNF‐α, PGE2 and MMP‐8 levels, however, the difference was not significant (p > .05). Pain scores were significantly lower in the cryotherapy group for the first 3 days (p < .05), except for 24th hours (p > .05).
Conclusions
The positive correlation between interappointment pain and IL‐1β and PGE2 levels might indicate that these biomarker levels can be used to predict the severity of post‐operative pain. Intracanal cryotherapy was effective in reducing post‐operative pain in the short term in teeth with asymptomatic apical periodontitis. Cryotherapy prevented an increase in IL‐1β, IL‐2 and IL‐6 levels compared with the control group.
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