Should an intercalated degree be compulsory for undergraduate medical students?

Undertaking an intercalated year whilst at medical school involves taking time out of the medicine undergraduate programme in order to pursue a separate but related degree. It is widely seen as a challenging but rewarding experience, with much to be gained from the independent project or research component of most additional degrees. However, whilst intercalating is encouraged at many universities and is incorporated into some undergraduate curricula, it is by no means compulsory for all students. The literature would suggest that those who have intercalated tend to do better academically, both for the remainder of medical school and after graduating. Despite this, the issue of making intercalation mandatory is one of considerable debate, with counter-arguments ranging from the detrimental effect time taken out of the course can have to the lack of options available to cater for all students. Nonetheless, the research skills developed during an intercalated year are invaluable and help students prepare for taking a critical evidence-based approach to medicine. If intercalated degrees were made compulsory for undergraduates, it would be a step in the right direction. It would mean the doctors of tomorrow would be better equipped to practise medicine in disciplines that are constantly evolving

Cytosolic thioredoxin reductase 1 is required for correct disulfide formation in the ER

Folding of proteins entering the secretory pathway in mammalian cells frequently requires the insertion of disulfide bonds. Disulfide insertion can result in covalent linkages found in the native structure as well as those that are not, so‐called non‐native disulfides. The pathways for disulfide formation are well characterized, but our understanding of how non‐native disulfides are reduced so that the correct or native disulfides can form is poor. Here, we use a novel assay to demonstrate that the reduction in non‐native disulfides requires NADPH as the ultimate electron donor, and a robust cytosolic thioredoxin system, driven by thioredoxin reductase 1 (TrxR1 or TXNRD1). Inhibition of this reductive pathway prevents the correct folding and secretion of proteins that are known to form non‐native disulfides during their folding. Hence, we have shown for the first time that mammalian cells have a pathway for transferring reducing equivalents from the cytosol to the ER, which is required to ensure correct disulfide formation in proteins entering the secretory pathway

Quinolones and their clinical relevance in the management of enteric fevers in the new millennium: Findings from a review of 55,853 Salmonella isolates

No Abstract

Impact of intermittent preventive treatment with dihydroartemisinin-piperaquine on malaria in Ugandan schoolchildren: a randomized, placebo-controlled trial.

BACKGROUND: Intermittent preventive treatment (IPT) in schoolchildren offers a promising option for malaria control. However, the optimal drug and dosing regimens for IPT remain to be determined. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 740 schoolchildren aged 6-14 years living in a setting of high malaria transmission in Uganda. Enrolled children were randomized to dihydroartemisinin-piperaquine (DP) given once a month (IPTm), DP given once a school term (4 treatments over 12 months, IPTst), or placebo and followed for 12 months. The primary outcome was the incidence of malaria over 12 months. Secondary outcomes included parasite prevalence and anemia over 12 months. Analyses were conducted on an intention-to-treat basis. RESULTS: In the placebo arm, the incidence of malaria was 0.34 episodes per person-year and the prevalence of parasitemia and anemia was 38% and 20%, respectively. IPTm reduced the incidence of malaria by 96% (95% confidence interval [CI], 88%-99%, P < .0001), the prevalence of asymptomatic parasitemia by 94% (95% CI, 92%-96%, P < .0001), and the prevalence of anemia by 40% (95% CI, 19%-56%, P < .0001). IPTst had no significant effect on the incidence of symptomatic malaria or the prevalence of anemia, but reduced the prevalence of asymptomatic parasitemia by 54% (95% CI, 47%-60%, P < .0001). CONCLUSIONS: Monthly IPT with DP offered remarkable protection against clinical malaria, parasitemia, and anemia in schoolchildren living in a high-malaria-transmission setting. CLINICAL TRIALS REGISTRATION: NCT01231880

Health poverty among people with type 2 diabetes mellitus (T2DM) in Malaysia

In the context of the escalating burden of diabetes in low and middle-income countries (LMICs), there is a pressing concern about the widening disparities in care and outcomes across socioeconomic groups. This paper estimates health poverty measures among individuals with type 2 diabetes mellitus (T2DM) in Malaysia. Using data from the National Diabetes Registry between 2009 and 2018, the study linked 932,855 people with T2DM aged 40–75 to death records. Cox proportional hazards models were used to estimate the 5-year survival probabilities for each patient, stratified by age and sex, while controlling for comorbidities and area-based indicators of socio-economic status (SES), such as district-level asset-based indices and night-time luminosity. Measures of health poverty, based on the Foster-Greer-Thorbecke (FGT) measures, were employed to capture excessive risk of premature mortality. Two poverty line thresholds were used, namely a 5% and 10% reduction in survival probability compared to age and sex-adjusted survival probability of the general population. Counterfactual simulations estimated the extent to which comorbidities contribute to health poverty. 43.5% of the sample experienced health poverty using the 5% threshold, and 8.9% were health poor using the 10% threshold. Comorbidities contribute 2.9% for males and 5.4% for females, at the 5% threshold. At the 10% threshold, they contribute 7.4% for males and 3.4% for females. If all patients lived in areas of highest night-light intensity, poverty would fall by 5.8% for males and 4.6% for females at the 5% threshold, and 4.1% for males and 0.8% for females at the 10% threshold. In Malaysia, there is a high incidence of health poverty among people with diabetes, and it is strongly associated with comorbidities and area-based measures of SES. Expanding the application of health poverty measurement, through a combination of clinical registries and open spatial data, can facilitate simulations for health poverty alleviation.</p

Odour-mediated orientation of beetles is influenced by age, sex and morph

The behaviour of insects is dictated by a combination of factors and may vary considerably between individuals, but small insects are often considered en masse and thus these differences can be overlooked. For example, the cowpea bruchid Callosobruchus maculatus F. exists naturally in two adult forms: the active (flight) form for dispersal, and the inactive (flightless), more fecund but shorter-lived form. Given that these morphs show dissimilar biology, it is possible that they differ in odour-mediated orientation and yet studies of this species frequently neglect to distinguish morph type, or are carried out only on the inactive morph. Along with sex and age of individual, adult morph could be an important variable determining the biology of this and similar species, informing studies on evolution, ecology and pest management. We used an olfactometer with motion-tracking to investigate whether the olfactory behaviour and orientation of C. maculatus towards infested and uninfested cowpeas and a plant-derived repellent compound, methyl salicylate, differed between morphs or sexes. We found significant differences between the behaviour of male and female beetles and beetles of different ages, as well as interactive effects of sex, morph and age, in response to both host and repellent odours. This study demonstrates that behavioural experiments on insects should control for sex and age, while also considering differences between adult morphs where present in insect species. This finding has broad implications for fundamental entomological research, particularly when exploring the relationships between physiology, behaviour and evolutionary biology, and the application of crop protection strategies

Incorporating chemical signalling factors into cell-based models of growing epithelial tissues

In this paper we present a comprehensive computational framework within which the effects of chemical signalling factors on growing epithelial tissues can be studied. The method incorporates a vertex-based cell model, in conjunction with a solver for the governing chemical equations. The vertex model provides a natural mesh for the finite element method (FEM), with node movements determined by force laws. The arbitrary Lagrangian–Eulerian formulation is adopted to account for domain movement between iterations. The effects of cell proliferation and junctional rearrangements on the mesh are also examined. By implementing refinements of the mesh we show that the finite element (FE) approximation converges towards an accurate numerical solution. The potential utility of the system is demonstrated in the context of Decapentaplegic (Dpp), a morphogen which plays a crucial role in development of the Drosophila imaginal wing disc. Despite the presence of a Dpp gradient, growth is uniform across the wing disc. We make the growth rate of cells dependent on Dpp concentration and show that the number of proliferation events increases in regions of high concentration. This allows hypotheses regarding mechanisms of growth control to be rigorously tested. The method we describe may be adapted to a range of potential application areas, and to other cell-based models with designated node movements, to accurately probe the role of morphogens in epithelial tissues

Cortical tau is associated with microstructural imaging biomarkers of neurite density and dendritic complexity in Alzheimer's disease

INTRODUCTION: In Alzheimer's disease (AD), hyperphosphorylated tau is closely associated with focal neurodegeneration, but the mechanism remains uncertain. METHODS: We quantified cortical microstructure using neurite orientation dispersion and density imaging in 14 individuals with young onset AD. Diffusion tensor imaging measured mean diffusivity (MD). Amyloid beta and tau positron emission tomography were acquired and associations with microstructural measures were assessed. RESULTS: When regional volume was adjusted for, in the medial temporal lobe there was a significant negative association between neurite density and tau (partial R2  = 0.56, p = 0.008) and between orientation dispersion and tau (partial R2  = 0.66, p = 0.002), but not between MD and tau. In a wider cortical composite, there was an association between orientation dispersion and tau (partial R2  = 0.43, p = 0.030), but not between other measures and tau. DISCUSSION: Our findings are consistent with tau causing first dendritic pruning (reducing dispersion/complexity) followed by neuronal loss. Advanced magnetic resonance imaging (MRI) microstructural measures have the potential to provide information relating to underlying tau deposition