Cystic fibrosis (CF) patients receive repeated courses of aminoglycoside therapy. These patients would consequently be expected to be more susceptible to cochleotoxicity, a recognized side effect with single courses of aminoglycoside therapy. The primary aim of this retrospective study was to establish the incidence and severity of auditory deficit in CF patients. Standard (0.25-to 8-kHz) and high-frequency (10-to 16-kHz) pure-tone audiometry was carried out in 70 CF patients, and the results were compared with the results from 91 control subjects. These subjects were further divided into pediatric and adult groups. Of 70 CF patients, 12 (1 pediatric) displayed hearing loss considered to be caused by repeated exposure to aminoglycosides. There was a nonlinear relationship between the courses of therapy received and the incidence of hearing loss. The severity of the loss did not appear to be related to the number of courses received. Assuming the risk of loss to be independent for each course, preliminary estimates of per course risk of hearing loss were less than 2%. Upon comparison with previous clinical studies and experimental work, these findings suggest that the incidence of cochleotoxicity in CF patients is considerably lower than would be expected, suggesting that the CF condition may confer protection against aminoglycoside cochleotoxicity.
We have proposed that since the type II pyrethroids deltamethrin and cypermethrin, but not the type I pyrethroid cismethrin act on chloride channels, this could contribute to the bimodal nature of pyrethroid poisoning syndromes. We now examine a wider range of pyrethroid structures on the activity of these calcium-independent voltage-gated maxi-chloride channels. Excised inside-out membrane patches from differentiated mouse neuroblastoma cells were used, and mean channel open probabilities calculated. For single dosing at 10 microM, bioallethrin, beta-cyfluthrin, cypermethrin, deltamethrin, and fenpropathrin were all found to significantly decrease open channel probability (p < 0.05). Bifenthrin, bioresmethrin, cispermethrin, cisresmethrin, cyfluthrin isomers 2 and 4, lambda-cyhalothrin, esfenvalerate, and tefluthrin, did not significantly alter open channel probability (p > 0.05). Since the type II pyrethroids, esfenvalerate, and lambda-cyhalothrin were ineffective, we must conclude that actions at the chloride ion channel target cannot in themselves account for the differences between the two types of poisoning syndrome. Sequential dosing with type II pyrethroids caused no further chloride ion channel closure. The type I pyrethroid cisresmethrin did however prevent a subsequent effect by the mixed type pyrethroid fenpropathrin. In contrast, the type I pyrethroid cispermethrin did not prevent a subsequent effect due to the type II pyrethroid deltamethrin. The difference in effect may be the result of differences in potency, as deltamethrin had a greater effect than fenpropathrin. It therefore appears clear that in some combinations the type I and type II pyrethroids can compete and may bind to the same chloride channel target site.
An extract of Mangifera pajang kernel has been previously found to contain a high content of antioxidant phytochemicals. The present research was conducted to investigate the anticancer potential of this kernel extract. The results showed that the kernel crude extract induced cytotoxicity in MCF-7 (hormone-dependent breast cancer) cells and MDA-MB-231 (non-hormone dependent breast cancer) cells with IC50 values of 23 and 30.5 microg/ml, respectively. The kernel extract induced cell cycle arrest in MCF-7 cells at the sub-G1 (apoptosis) phase of the cell cycle in a time-dependent manner. For MDA-MB-231 cells, the kernel extract induced strong G2-M arrest in cell cycle progression at 24h, resulting in substantial sub-G1 (apoptosis) arrest after 48 and 72 h of incubation. Staining with Annexin V-FITC and propidium iodide revealed that this apoptosis occurred early in both cell types, 36 h for MCF-7 cells and 24 h for MDA-MB-231 cells, with 14.0% and 16.5% of the cells respectively undergoing apoptosis at these times. This apoptosis appeared to be dependent on caspase-2 and -3 in MCF-7 cells, and on caspase-2, -3 and -9 in MDA-MB-231 cells. These findings suggest that M. pajang kernel extract has potential as a potent cytotoxic agent against breast cancer cell lines.
The authors describe and evaluate a method to motivate medical students to maximize the effectiveness of dissection opportunities by using In-Course-Assessments (ICAs) to encourage teamwork. A student's final mark was derived by combining the group dissection mark, group mark for questions, and their individual question mark. An analysis of the impact of the ICA was performed by comparing end of module practical summative marks in student cohorts who had, or had not, participated in the ICAs. Summative marks were compared by two-way ANOVA followed by Dunnets test, or by repeated measures ANOVA, as appropriate. A cohort of medical students was selected that had experienced both practical classes without (year one) and with the new ICA structure (year two). Comparison of summative year one and year two marks illustrated an increased improvement in year two performance in this cohort. A significant increase was also noted when comparing this cohort with five preceding year two cohorts who had not experienced the ICAs (P <0.0001). To ensure that variation in the practical summative examination was not impacting on the data, a comparison was made between three cohorts who had performed the same summative examination. Results show that students who had undertook weekly ICAs showed significantly improved summative marks, compared with those who did not (P <0.0001). This approach to ICA promotes engagement with learning resources in an active, team-based, cooperative learning environment.
The ability to find, interpret and use information is a key skill in any clinician's arsenal. During medical training, we aim to equip our students with the ability to navigate the potentially baffling amount of information available online, and come to valid conclusions. This article reflects on the nature of research skills and how they are delivered in medical education. It also explores whether these are the most efficient methods for enabling students to become able researchers. Comparisons with other types of university degrees are made, and consideration given to how research skills should best be integrated into our teaching.Keywords: research skills; transferable skills; life-long learning; employability How can we best prepare our students to enquire, evaluate and be life-long learners?Research skills are required in all branches of medicine (Laidlaw et al., 2012). Clinicians need to be lifelong learners, able to evaluate evidence and understand the process of scientific enquiry. Whether or not a doctor pursues a research career, they still need to be able to make sense, and be critical, of the huge amount of information available online. They may also be required to carry out their own research study, and the training we provide should lay the foundations for them to develop their own rigorous and informed approaches to research.Knowledge, skills and behaviours can be absorbed by students without them noticing, and it is only when the values they are exposed to conflict with their own that they become conscious they have been taught covertly (Phillips, 2013). This approach to conveying information may be more appropriate for some transferable skills than others, and carries the danger that values can be imparted on students without them considering if they fully agree with or understand them. Research skills include tangible principles that can be taught more visibly; like good study design and the scientific method. Evidence suggests that we are more likely to recognise having learned something if we are told explicitly that we will be learning it (Murdoch-Eaton et al., 2010). In addition, enabling students to be more aware of their own skillsets may well be important for employability, as they will be able to communicate these skillsets to potential employers when applying for jobs. In a typical academic setting, teachers may have spent decades with research as their primary activity. In contrast, the students' primary activity is to learn and understand medical knowledge. Thus, we may need to be more overt about research skills and explain their impact on employment within our curricula so that the students can understand what they are learning, and why. As educators, we must understand the perceptions of research that students have when they enrol in medical school. Most of our medical students are high-achievers, previously attaining high grades by learning and recalling facts. A UK study found that whilst school pupils are generally familiar with the idea of research, for example in form...
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