In Vitro Interactions of Antifungal Agents and Everolimus Against Aspergillus Species.

Multiple cellular activities, including protein and lipid synthesis, ribosome biogenesis, and metabolic processes, are regulated by the target of rapamycin (TOR) pathway. Recent research suggests that the TOR might play an important role in various physiological functions of pathogenic fungi, such as nutrient sensing, stress response, and cell cycle progression. Given their robust immunosuppressant and antitumor activities, TOR inhibitors are widely used in clinical settings. In the present study, a microdilution checkerboard-based approach was employed to assess the interactions between the oral mammalian target of rapamycin (mTOR) inhibitor everolimus (EVL) and antifungal agents in the treatment of Aspergillus species derived from 35 clinical isolates in vitro. The results revealed that EVL exhibited promising inhibitory synergy with itraconazole (ITC), posaconazole (POS), and amphotericin B (AMB) for 85.7%, 74.2%, and 71.4%, respectively. In contrast, EVL exhibited minimal synergistic inhibitory activity (14.3%) when applied in combination with voriconazole (VRC). Antagonistic interactions were not observed. In vivo experiments conducted in Galleria mellonella revealed that EVL in combination with antifungal agents improved the larva survival rates in the ITC, VRC, POS, and AMB groups by 18.3%, 13.3%, 26.7%, and 13.3%, respectively. These data suggest that the combination treatment with antifungal agents and antifungal agents holds promise as a means of alleviating clinical aspergillosis.

Independent risk factors for morphological abnormalities of the internal carotid artery.

PURPOSE: Whether carotid abnormalities (CAs) are congenital or acquired, and whether they are risk factors for cerebrovascular diseases or medical curiosities, is still under debate. The aim of this study was to identify the independent risk factors for CAs. METHODS: In this study, subjects (aged 3 days to 102 years) were divided into nine age groups, divided by 10-year intervals. The observed CAs were prospectively classified, according to the nature of the abnormality. Analyses of the factors associated with CAs were performed by univariate and multivariate logistic regression models. RESUITS: Of the 1,838 internal carotid arteries studied, 552 had CA (30%). There were peaks in the prevalence of CA in the 0-9-year-old group and in the above 80 years group; the lowest rate was found among the subjects in the 20-39-year-old group. The significant predictors of CA were age (OR 1.986, in the60-69-year-old group; OR 2.283, in the 70-79-year-old group; and OR 3.566, in the > 80-year-old group vs the 40-49-year-old group reference group), female gender (OR 1.799), hypertension (OR 1.52), and carotid artery atherosclerosis (OR3.176). CAs in youngersubjects were also associated with age (OR 9.894 in the 0-9-year-old group; and OR 3.294 in the 10-19-year-old group vs the 30-39-year-old group reference group). CONCLUSIONS: Both congenital and acquired factors may be involved in CAs. In subjects> or = 40years old, CAs seem to be more associated with acquired factors, including ageing, gender, hypertension, and atherosclerosis.

Combined linear array high- and convex array low-frequency duplex ultrasonography with or without examination of the ophthalmic artery in the differential diagnosis of occlusion from severe stenosis of internal carotid artery.

PURPOSE: To assess the benefits of using a low-frequency convex probe and detecting ophthalmic artery blood flow for the differential diagnosis of occlusion from severe stenosis of the internal carotid artery (ICA). METHODS: A total of 103 patients were enrolled and had three sequential examinations by an experienced sonographer. First, the proximal ICA was examined with a 5.0-7.5-MHz linear probe. Second, the distal ICA was examined with a 3.5-5.0-MHz convex probe. Third, the ophthalmic artery (OA) was examined with a 5.0-7.5-MHz linear probe. Three parallel sets of diagnoses were made based on results from (1) high-frequency ultrasonography; (2) combined use of high- and low-frequency ultrasonography; and (3) combined use of high- and low-frequency ultrasonography along with OAs examination findings. Efficiencies of the three diagnoses were compared by receiver operating characteristic curves with digital subtraction angiography as the gold standard. RESULTS: The second diagnostic approach yielded the highest sensitivity (96.6%) and specificity (94.5%). OA blood flow was reversed in most, but not all, cases of ICA occlusion (27/29). Areas under the receiver operating characteristic curves of the three diagnoses were significantly different (p < 0.05). CONCLUSIONS: The diagnostic performance of combined high- and low-frequency ultrasonography is greater than that of high-frequency ultrasonography alone. Although OA examination does not increase the diagnostic performance, it provides helpful data for the assessment of hemodynamics and collateral circulation.

Morphological features of the internal carotid artery: advantages of combining linear and convex probes in duplex ultrasonography.

RATIONALE AND OBJECTIVES: Previous research has determined that carotid abnormalities (CAs) are partly located >3 cm above the carotid bifurcation. However, identifying CAs occurring in this location using high-frequency linear probes is difficult. The aim of this study was to explore the efficacy of a combination of high-frequency and low-frequency probes in duplex ultrasonography for identifying morphologic features of the internal carotid artery (ICA). MATERIALS AND METHODS: A total of 1055 ICAs from 532 patients were analyzed. CAs were classified prospectively according to the criteria of Wain et al, Weibel and Fields, and Metz et al. The diagnostic rates of high-frequency ultrasonography alone and a combination of high-frequency and low-frequency ultrasonography were compared. The distances from the carotid bifurcation to the initial point of the CA and to the mandibular angle were also measured. RESULTS: High-frequency ultrasonography detected 23.2% of CAs, and the combination detected 32.2% of CAs (P < .001) in the 1055 ICAs. Of these CAs, 32.4% and 16.8% began >2.5 and >3 cm above the carotid bifurcation, respectively. The distance between the carotid bifurcation and the mandibular angle was <1.5 cm in 100 arteries (9.48%). The diameter of the distal ICA was larger in patients with CAs than in those without CAs (4.33 ± 0.52 vs 4.13 ± 0.49 mm, P < .001). CONCLUSIONS: Combining high-frequency and low-frequency probes is better than high-frequency probes alone to assess morphologic features of the ICA in duplex ultrasonography. Low-frequency convex probes should be added to traditional ultrasonography for the evaluation of morphologic features of the ICA before carotid endarterectomy, carotid artery stenting, and CA angioplasty.