Translation of the Amsterdam Preoperative Anxiety and Information Score (APAIS) into the Amharic Version and Its Validation for Evaluation of Preoperative Anxiety.

BACKGROUND: Peri-operative anxiety is a vague, unpleasant feeling, the source of which is often nonspecific and unknown to the individual. It affects all aspects of anesthesia. Although the magnitude and consequences of preoperative anxiety are well documented in the developed world, there are limited studies conducted in Ethiopia. The primary aim of this study is to produce the Amharic version of APAIS and evaluate its validity in assessing the prevalence of preoperative anxiety in surgical patients. METHODS: A cross-cultural adaptation process using a forward/backward translation of the APAIS scale was performed. The Amharic version was then tested in 365 sampled elective adult surgical patients scheduled for surgery at Tikur Anbessa specialized Hospital. The validity of the translated version was also checked by evaluating its psychometric properties of internal validity and acceptability. RESULT: The results showed that the reliability of the APAIS-Amharic was high (Cronbach's alpha of 0.87) and the data collected was a good fit (RMSEA of 0.04). In addition, the questionnaire was well-accepted 100% with no missing values for each dimension of the APAIS. The mean APAIS scores for total anxiety and desire for information were 11.6 and 6.0 respectively and 58.9% of the study participants had anxiety and those patients, who had some form of formal education, came from urban areas, had previous anesthesia experience and complications and who had average or high information requirement was more likely to be anxious. CONCLUSION: APAIS-Amharic is a reliable and acceptable tool for measuring patients' preoperative anxiety and their need for information. It can be used routinely as a screening instrument at pre-anesthesia clinics to assess patients' level of anxiety.

Building regional anesthesia capacity in limited-resource settings: a pilot study evaluating a 4-week curriculum.

Aim: To pilot a 4-week regional anesthesia curriculum for limited-resource settings. Intervention: A baseline needs assessment and knowledge test were deployed. The curriculum included lectures and hands-on teaching, followed by knowledge attainment tests. Results: Scores on the knowledge test improved from a mean of 37.1% (SD 14.7%) to 50.9% (SD 18.6%) (p = 0.017) at 4 weeks and 49% at 24 months. An average of 1.7 extremity blocks per month was performed in 3 months prior to the curriculum, compared with an average of 4.1 per month in 8 months following. Conclusion: This collaborative curriculum appeared to have a positive impact on the knowledge and utilization of regional anesthesia.

Airway epithelial stem cell chimerism in cystic fibrosis lung transplant recipients.

BACKGROUND: The conducting airway epithelium is repaired by tissue specific stem cells (TSC). In response to mild/moderate injury, each TSC repairs a discrete area of the epithelium. In contrast, severe epithelial injury stimulates TSC migration and expands the stem cell's reparative domain. Lung transplantation (LTx) can cause a moderate/severe airway injury and the remodeled airway contains a chimeric mixture of donor and recipient cells. These studies supported the hypothesis, LTx stimulates TSC migration resulting in epithelial chimerism. We tested this hypothesis in cystic fibrosis (CF) LTx patients. METHODS: Airway mucosal injury was quantified using bronchoscopic imaging and a novel grading system. Bronchial brushing was used to recover TSC from 10 sites in the recipient and allograft airways. TSC chimerism was quantified by short tandem repeat analysis. TSC self-renewal and differentiation potential were assayed using the clone forming cell frequency and air-liquid-interface methods. Electrophysiology was used to determine if TSC chimerism altered epithelial ion channel activity. RESULTS: LTx caused a mild to moderate airway mucosal injury. Donor and recipient TSC were identified in 91% of anastomotic sites and 93% of bronchial airways. TSC chimerism did not alter stem cell self-renewal or differentiation potential. The frequency of recipient TSC was proportional to CF Transmembrane Conductance Regulator (CFTR)-dependent ion channel activity and 33% of allograft regions were at risk for abnormal CFTR activity. CONCLUSIONS: LTx in CF patients stimulates bidirectional TSC migration across the anastomoses. TSC chimerism may alter ion homeostasis and compromise the host defense capability of the allograft airway epithelium.

Cell Therapy for Cystic Fibrosis Lung Disease: Regenerative Basal Cell Amplification.

The human airway epithelium is regenerated by basal cells. Thus, basal cell therapy has the potential to cure cystic fibrosis (CF) lung disease. We previously reported that the human basal cells repopulated the mouse airway epithelium after transplantation, and we estimated that 60 million cells would be needed to treat a human patient. To further develop cell therapy, we compared the proliferation potential of non-CF and CF tissue-derived bronchial basal cells. Three methods were used: regenerative cell frequency, burst size, and cell division frequency. Second, we used a serial passage strategy to determine if CF basal cells could be amplified to the estimated therapeutic dose. These studies evaluated that tissue-derived bronchial basal cells and the basal cells that were recovered by brushing bronchial airways or the nasal respiratory epithelium. Finally, we used the limiting dilution method to isolate non-CF and CF basal cell clones. The proliferation assays and the air-liquid-interface differentiation method were used to determine if cell amplification altered the proliferation and/or differentiation potential of clonal isolates. We demonstrate that: (a) non-CF and CF basal cell proliferation is similar, (b) CF basal cells can be amplified to a therapeutic cell dose, and (c) amplified non-CF and CF basal cell clones differentiate normally. Despite these encouraging findings, we also find that the cell amplification process depletes the regenerative basal cell pool. Analysis of basal cell clones indicates that serial passage selects for long-lived basal cells and raise the possibility that prospective isolation of these stem-like cells will improve the efficacy of cell replacement therapy. Stem Cells Translational Medicine 2019;8:225&235.

An assessment of the relative contributions of redox and steric issues to laccase specificity towards putative substrates.

Laccases catalyze the one-electron oxidation of a broad range of substrates coupled to the 4 electron reduction of O2 to H2O. Phenols are typical substrates, because their redox potentials (ranging from 0.5 to 1.0 V vs. NHE) are low enough to allow electron abstraction by the T1 Cu(II) that, although a relatively modest oxidant (in the 0.4-0.8 V range), is the electron-acceptor in laccases. The present study comparatively investigated the oxidation performances of Trametes villosa and Myceliophthora thermophila laccases, two enzymes markedly differing in redox potential (0.79 and 0.46 V). The oxidation efficiency and kinetic constants of laccase-catalyzed conversion of putative substrates were determined. Hammett plots related to the oxidation of substituted phenols by the two laccases, in combination with the kinetic isotope effect determination, confirmed a rate-determining electron transfer from the substrate to the enzyme. The efficiency of oxidation was found to increase with the decrease in redox potential of the substrates, and the Marcus reorganisation energy for electron transfer to the T1 copper site was determined. Steric hindrance to substrate docking was inferred because some of the phenols and anilines investigated, despite possessing a redox potential compatible with one-electron abstraction, were scarcely oxidised. A threshold value of steric hindrance of the substrate, allowed for fitting into the active site of T. villosa laccase, was extrapolated from structural information provided by X-ray analysis of T. versicolor lac3B, sharing an identity of 99% at the protein level, thus enabling us to assess the relative contribution of steric and redox properties of a substrate in determining its susceptibility to laccase oxidation. The inferred structural threshold is compatible with the distance between two phenylalanine residues that mark the entrance to the active site. Interaction of the substrate with other residues of the active site is commented on.