9 research outputs found
The Glucocorticoid Receptor and Certain KRÜPPEL-Like Transcription Factors have the Potential to Synergistically Stimulate Bovine Herpesvirus 1 Transcription and Reactivation from Latency
Bovine herpesvirus 1 (BoHV-1), an important bovine pathogen, establishes life-long latency in sensory neurons within trigeminal ganglia (TG). Stress, as mimicked by the synthetic corticosteroid dexamethasone, consistently induces reactivation in calves latently infected with BoHV-1. Dexamethasone induces expression of several transcription factors in TG neurons during early stages of reactivation, including Krüppel-like transcription factors (KLF): KLF4, KLF6, KLF15, and promyelocytic leukemia zinc finger. Furthermore, the glucocorticoid receptor (GR) is consistently detected in TG neurons expressing viral regulatory proteins during reactivation from latency. The viral immediate early transcription unit 1 (IEtu1) promoter that drives expression of two viral transcription factors (bICP0 and bICP4) contains two GR response elements (GREs) and is stimulated by DEX. KLF15 and the GR form a feed forward transcription loop that synergistically stimulates productive infection and IEtu1 promoter activity. New studies demonstrate the GR and KLF6 synergistically stimulate productive infection and IEtu1 promoter activity if the GREs are intact. Furthermore, the GR and KLF6 interact with wild-type GREs within the IEtu1 promoter, but not GRE mutants. These studies suggest that certain KLF family members and the GR can convert a silent viral genome in latently infected neurons into an actively transcribing genome during reactivation from latency
EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial
More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
In vitro production of Sudanese camel (Camelus dromedarius) embryos from epididymal spermatozoa and follicular oocytes of slaughtered animals
Application of assisted reproductive technology in camelidea, such as artificial insemination (AI) and embryo transfer, has been slow in comparison to that for other livestock species. In Egypt, there are few attempts to establish in vitro maturation (IVM) and fertilization (IVF) techniques in dromedary camel. The present study was carried out to produce Sudanese camel embryos using in vitro matured oocytes and epididymal spermatozoa. Dromedary camel ovaries were collected from abattoirs and then, the oocytes were aspirated from all the visible follicles on the ovarian surface (~2-8 mm in a diameter). Meanwhile, Fetal Dromedary Camel Serum (FDCS) was obtained from camel fetuses after slaughtering. Thereafter, only Cumulus Oocyte Complexes (COCs) were matured in vitro in the Tissue Culture Medium (TCM-199) complemented with 10% FDCS. Spermatozoa required for in vitro fertilization were collected from testes (epididymal cauda) of the slaughtered camel bulls. The results clearly showed that the maturation rate of oocytes at metaphase II was about 59.5% while the fertilization rate was around 70.4%. Intriguingly, the embryo rates determined were 13.1%, in 2-cell; 0.0%, in 4-cell; 34.7%, in 8-16% cell; 39.1%, in morula and 13.1% in a blastocyst stage. This study represented a successful in vitro production of Sudanese dromedary camel embryos from epididymal sperm cells and in vitro matured oocytes recovered from slaughtered camels
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Safety and Efficacy of Evacetrapib in Patients with Inadequately-controlled Hypercholesterolemia and High Cardiovascular Risk; A meta-analysis of Randomized Placebo-controlled Trials
•Evacetrapib could significantly increases the HDL and Apo-A1 levels.•Evacetrapib could significantly decreases the LDL cholesterol and Apo-B levels.•Evacetrapib associated with lower risk of total AEs.•Evacetrapib was not associated with prolonged QT interval.•Evacetrapib was able to gain trust after the off-target side effects of torcetrapib.
Low-density lipoprotein cholesterol (LDL-C) is causally related to cardiovascular disease. Inhibition of cholesteryl ester transfer protein with Evacetrapib may provide an additional treatment option for patients who do not reach their LDL-C goal with statins or patients who cannot tolerate statins. We aimed to evaluate the safety and efficacy of Evacetrapib in patients with inadequately-controlled hypercholesterolemia and high cardiovascular risk.
A computer literature search for PubMed, Scopus, and Science Direct was carried out from inception to 2019 and was updated from January 2019 till March 2021. We included only RCTs. Data were pooled as a mean difference in a random-effect model using the Mantel-Haenzel (M-H) method. We used Open Meta [Analyst] software (by the center of evidence-based medicine, Oxford University, UK).
Five studies (n = 12,937 patients) reported in five articles were included in this meta-analysis. The overall pooled estimate showed that LDL-C was significantly lower in the evacetrapib group than the placebo group (MD -34.07 mg/dL, 95% CI [-40.66, -27.49], p<0.0001). The pooled estimate showed that Apo-B was significantly lower in the evacetrapib130 mg group than the placebo group (MD -22.64 mg/dL, 95% CI [-30.70, -14.58], p<0.0001). HDL-C was significantly higher in the evacetrapib group over the placebo group (MD 93.31 mg/dL, 95% CI [56.07, 130.56], p<0.0001).
Current evidence from five RCTs (12,539 participants) suggests that evacetrapib has favorable outcomes in patients with inadequately-controlled Hypercholesterolemia and high cardiovascular risks. Evacetrapib could significantly increase the HDL and Apo-A1 levels and lower the LDL cholesterol and Apo-B levels with an acceptable safety profile
Detecting Clay Minerals in Hydrothermal Alteration Areas with Integration of ASTER Image and Spectral Data in Kösedag-Zara (Sivas), Turkey
New Benzodioxole-based Pyrazoline Derivatives: Synthesis and Anticandidal, In silico ADME, Molecular Docking Studies
EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI): Study protocol for a multicentre, observational trial
Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369.