Predictive validity of the UK clinical aptitude test in the final years of medical school:a prospective cohort study

Peer reviewedPublisher PD

Application of the speed-duration relationship to normalize the intensity of high-intensity interval training

The tolerable duration of continuous high-intensity exercise is determined by the hyperbolic Speed-tolerable duration (S-tLIM) relationship. However, application of the S-tLIM relationship to normalize the intensity of High-Intensity Interval Training (HIIT) has yet to be considered, with this the aim of present study. Subjects completed a ramp-incremental test, and series of 4 constant-speed tests to determine the S-tLIM relationship. A sub-group of subjects (n = 8) then repeated 4 min bouts of exercise at the speeds predicted to induce intolerance at 4 min (WR4), 6 min (WR6) and 8 min (WR8), interspersed with bouts of 4 min recovery, to the point of exercise intolerance (fixed WR HIIT) on different days, with the aim of establishing the work rate that could be sustained for 960 s (i.e. 4×4 min). A sub-group of subjects (n = 6) also completed 4 bouts of exercise interspersed with 4 min recovery, with each bout continued to the point of exercise intolerance (maximal HIIT) to determine the appropriate protocol for maximizing the amount of high-intensity work that can be completed during 4×4 min HIIT. For fixed WR HIIT tLIM of HIIT sessions was 399±81 s for WR4, 892±181 s for WR6 and 1517±346 s for WR8, with total exercise durations all significantly different from each other (P<0.050). For maximal HIIT, there was no difference in tLIM of each of the 4 bouts (Bout 1: 229±27 s; Bout 2: 262±37 s; Bout 3: 235±49 s; Bout 4: 235±53 s; P>0.050). However, there was significantly less high-intensity work completed during bouts 2 (153.5±40. 9 m), 3 (136.9±38.9 m), and 4 (136.7±39.3 m), compared with bout 1 (264.9±58.7 m; P>0.050). These data establish that WR6 provides the appropriate work rate to normalize the intensity of HIIT between subjects. Maximal HIIT provides a protocol which allows the relative contribution of the work rate profile to physiological adaptations to be considered during alternative intensity-matched HIIT protocols

An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds

Background Endogenous nitric oxide (NO) kills bacteria and other organisms as part of the innate immune response. When nitrite is exposed to low pH, NO is generated and has been used as an NO delivery system to treat skin infections. We demonstrated eradication of MRSA carriage from wounds using a topical formulation of citric acid (4.5%) and sodium nitrite (3%) creams co-applied for 5 days to 15 wounds in an observational prospective pilot study of 8 patients. Findings Following treatment with topical citric acid and sodium nitrite, 9 of 15 wounds (60%) and 3 of 8 patients (37%) were cleared of infection. MRSA isolates from these patients were all sensitive to acidified nitrite in vitro compared to methicillin-sensitive S. aureus and a reference strain of MRSA. Conclusions Nitric oxide and acidified nitrite offer a novel therapy for control of MRSA in wounds. Wounds that were not cleared of infection may have been re-contaminated or the bioavailability of acidified nitrite impaired by local factors in the tissue

The luminosity function of field galaxies

Schmidt's method for construction of luminosity function of galaxies is generalized by taking into account the dependence of density of galaxies from the distance in the near Universe. The logarithmical luminosity function (LLF) of field galaxies depending on morphological type is constructed. We show that the LLF for all galaxies, and also separately for elliptical and lenticular galaxies can be presented by Schechter function in narrow area of absolute magnitudes. The LLF of spiral galaxies was presented by Schechter function for enough wide area of absolute magnitudes: . Spiral galaxies differ slightly by parameter . At transition from early spirals to the late spirals parameter in Schechter function is reduced. The reduction of mean luminosity of galaxies is observed at transition from elliptical galaxies to lenticular galaxies, to early spiral galaxies, and further, to late spiral galaxies, in a bright end, . The completeness and the average density of samples of galaxies of different morphological types are estimated. In the range the mean number density of all galaxies is equal 0.127 Mpc-3.Comment: 14 page, 8 figures, to appear in Astrophysic

Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes

Cell-cycle progression and cell division in eukaryotes are governed in part by the cyclin family and their regulation of cyclin-dependent kinases (CDKs). Cyclins are very well characterised in model systems such as yeast and human cells, but surprisingly little is known about their number and role in Plasmodium, the unicellular protozoan parasite that causes malaria. Malaria parasite cell division and proliferation differs from that of many eukaryotes. During its life cycle it undergoes two types of mitosis: endomitosis in asexual stages and an extremely rapid mitotic process during male gametogenesis. Both schizogony (producing merozoites) in host liver and red blood cells, and sporogony (producing sporozoites) in the mosquito vector, are endomitotic with repeated nuclear replication, without chromosome condensation, before cell division. The role of specific cyclins during Plasmodium cell proliferation was unknown. We show here that the Plasmodium genome contains only three cyclin genes, representing an unusual repertoire of cyclin classes. Expression and reverse genetic analyses of the single Plant (P)-type cyclin, CYC3, in the rodent malaria parasite, Plasmodium berghei, revealed a cytoplasmic and nuclear location of the GFP-tagged protein throughout the lifecycle. Deletion of cyc3 resulted in defects in size, number and growth of oocysts, with abnormalities in budding and sporozoite formation. Furthermore, global transcript analysis of the cyc3-deleted and wild type parasites at gametocyte and ookinete stages identified differentially expressed genes required for signalling, invasion and oocyst development. Collectively these data suggest that cyc3 modulates oocyst endomitotic development in Plasmodium berghei

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

Proteomic identification of immunodiagnostic antigens for <i>Trypanosoma vivax </i>infections in cattle and generation of a proof-of-concept lateral flow test diagnostic device

Trypanosoma vivax is one of the causative agents of Animal African Trypanosomosis in cattle, which is endemic in sub-Saharan Africa and transmitted primarily by the bite of the tsetse fly vector. The parasite can also be mechanically transmitted, and this has allowed its spread to South America. Diagnostics are limited for this parasite and in farm settings diagnosis is mainly symptom-based. We set out to identify, using a proteomic approach, candidate diagnostic antigens to develop into an easy to use pen-side lateral flow test device. Two related members the invariant surface glycoprotein family, TvY486_0045500 and TvY486_0019690, were selected. Segments of these antigens, lacking N-terminal signal peptides and C-terminal transmembrane domains, were expressed in E. coli. Both were developed into ELISA tests and one of them, TvY486_0045500, was developed into a lateral flow test prototype. The tests were all evaluated blind with 113 randomised serum samples, taken from 37 calves before and after infection with T. vivax or T. congolense. The TvY486_0045500 and TvY486_0019690 ELISA tests gave identical sensitivity and specificity values for T. vivax infection of 94.5% (95% CI, 86.5% to 98.5%) and 88.0% (95% CI, 75.7% to 95.5%), respectively, and the TvY486_0045500 lateral flow test prototype a sensitivity and specificity of 92.0% (95% CI, 83.4% to 97.0%) and 89.8% (95% CI, 77.8% to 96.6%), respectively. These data suggest that recombinant TvY486_0045500 shows promise for the development of a pen-side lateral flow test for the diagnosis of T. vivax animal African trypanosomosis