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Bauer McKee posted an update 6 months, 1 week ago
The accuracy of the 4 topographic assessments in determining the centre coordinates of the MCL with respect to SL assessment was good no differences were found in the left eyes and although in the right eyes a more temporal and superior position of MCLs was determined (paired t-test, p less then 0.05) the difference was clinically negligible (0.16 ± 0.36 mm horizontally, 0.23 ± 0.48 vertically). Amongst the 4 practitioners one-way Anova for repeated measures showed no differences for any of the 3 manual assessments. Intra-class correlation coefficient was calculated among the 3 readings for each manual procedure and was very good (between 0.75 and 0.98) in 3 practitioners and moderate (between 0.49 and 0.92) in the fourth. CONCLUSIONS The assessment of MCL centration by performing corneal topography over the MCL is an accurate method. Furthermore, inter and intra-practitioner reliability showed by manual procedures appeared very good. PURPOSE To examine the influence of short-term fenestrated scleral lens wear on intraocular pressure (IOP) in healthy eyes. selleck compound METHODS IOP was measured before, during, and after a brief period (1-2 min) of fenestrated, scleral lens wear, using a rebound tonometer, in fifty, young healthy adults (mean age 23 ± 4 years) with normal corneas. RESULTS Immediately following lens insertion, 48 of the 50 (96 %) of participants displayed an increase in IOP (mean ± SD increase in these participants of 3.8 ± 2.0 mmHg). Immediately following lens removal, 50 % of participants displayed a reduction in IOP, equal to or lower than, the pre-insertion IOP (-1.0 ± 0.8 mmHg lower than baseline). The remaining 50 % of participants displayed an IOP slightly greater than the pre-insertion IOP (1.6 ± 1.0 mmHg greater) after lens removal. CONCLUSIONS Short-term fenestrated scleral lens wear resulted in a small, but statistically significant, increase in IOP in 96 % of young healthy participants ( less then 4 mmHg on average), which decreased to a level similar to pre-lens insertion IOP levels immediately following lens removal. Further research is required to determine if this measured change in IOP during scleral lens wear is artefactual, or an elevation in the true IOP. Endoscopic approaches for septal perforation closure have achieved a certain popularity. Many of the flaps described provide unilateral closure of the perforation. Thus, complete restoration of the normal multilayer septal anatomy is still challenging, particularly in children. This article presents a modified technique for endoscopic bilateral surgical repair of nasal septal perforations. A novel cross-septal returned flap was performed in nine patients with nasal septal perforations. The mean size of the perforation was 17.7mm in the sagittal axis and 16.9mm in the vertical axis. All patients were followed up for a minimum of 12 months (range 12-31 months). There was only one case of residual septal perforation during the follow-up period, but with a significant decrease in the severity of symptoms. The results of the surgical technique presented show its high efficacy. We believe that the best indication for this technique is non-epithelized perforation edges that cannot be used as a reliable bridge for the preparation of any cross-over flaps. Use of the cross-septal returned flap allows the complete bilateral repair of nasal septal perforations to be achieved. Antimicrobial stewardship programs (ASP) for oral antibiotics is still uncommon, despite the fact that oral antibiotics prescription accounts for 90% of total antibiotic consumption in developed countries. We introduced preauthorization and prospective audit and feedback (PAF) system on broad-spectrum oral antimicrobials as a part of ASP intervention from October 2015 in a tertiary children’s hospital in Japan. Antimicrobial consumption and cost of targeted oral antimicrobials decreased from 11.1 days of therapy (DOT) per 1000 outpatient visits and 860,040 yen ($ 7167 1 $ = 120 yen) to 1.9 DOT per 1000 outpatient visits and 142,200 yen ($ 1185) annually, respectively (p less then 0.001). Interrupted time-series analysis showed that prescriptions for targeted antimicrobials decreased rapidly after initiation of preauthorization (p less then 0.001). Prescriptions for non-targeted oral antimicrobial increased temporarily (p less then 0.001), but a decreasing trend was found after the initiation (p less then 0.001). In pre-intervention period, the main indications for using targeted antimicrobials were upper and lower respiratory infection, urinary tract infections, prophylaxis for medical procedures and otitis media, but only 21.4% of them were appropriate prescription. The appropriate prescription rate of post -intervention period increased to 58.5%. During the study period, the susceptibility pattern of major bacteria to these antimicrobials did not change. In conclusion, introduction of the preauthorization and PAF for selected oral antimicrobials decreased the antimicrobial use of both targeted and non-targeted antimicrobials. This intervention may be an effective method of ASP for other children’s hospitals. Currently, synergistic inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) and histone deacetylases (HDACs) has been a potential effective strategy for cancer treatment. Herein, by combining critical pharmacophores in approved drugs olaparib and chidamide, a series of novel 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid derivatives were designed and synthesized. All efforts led to a good dual PARP-1/HDAC-1 inhibitor, compound 4, with IC50 values of 4.2 and 340 nM against PARP-1 and HDAC-1, which were as potent as olaparib and chidamide respectively. The MTT assay further demonstrated that compound 4 had potent inhibitory activities against BRCA1/2-proficient K562 and MDA-MB-231 cells with GI50 values of 5.6 and 4.3 μM, respectively. Therefore, our results suggested that compound 4 could be a promising dual PARP-1/HDAC-1 inhibitor for further studies. In addition, a few excellent PARP-1 inhibitors such as 7-9 and HDAC-1 inhibitors such as 12 were serendipitously discovered, which also could be further studied in our next work.
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