CD4 cell count and viral load monitoring in patients undergoing antiretroviral therapy in Uganda: cost effectiveness study

Objective To examine the cost and cost effectiveness of quarterly CD4 cell count and viral load monitoring among patients taking antiretroviral therapy (ART)

Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial

Objective To evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda

Roles of discharge and temperature in recruitment of a cold-water fish, the European grayling Thymallus thymallus, near its southern range limit

Recruitment of salmonids is a result of density-dependent factors, specifically egg production in the previous year, and density-independent environmental processes driven by discharge and temperature. With the plethora of knowledge on major drivers of Atlantic salmon Salmo salar and brown trout Salmo trutta recruitment, there is a requirement to explore less known species, such as European grayling Thymallus thymallus, whose postemergence time coincides with period of increasing temperature and low discharge. This study assessed drivers of grayling recruitment in a southern English chalk stream, a system vulnerable to discharge and temperature alterations under future climate change predictions. The analyses explored age 0+ grayling survival in relation to conspecific and heterospecific densities and discharge- and temperature-derived factors. The final mixed-effects model revealed a positive relationship between age 0+ grayling survival and incubation temperature anomaly and age 0+ trout abundance. Similarly, postincubation temperature anomaly had a positive effect on 0+ grayling survival, but only up to a threshold temperature of 13.5°C, beyond which it had a negative effect. In contrast, increasing number of days with low discharge postincubation negatively influenced age 0+ grayling survival, with no evidence of an effect of elevated discharges following spawning. Our results emphasise the importance of maintaining natural discharge regimes in salmonid rivers by tackling multiple stressors operating at the catchment scale, including land and water use to mitigate for predicted climate driven changes. In addition, further research on recruitment drivers in less stable, rain-fed systems, is required

Ordered binary trees constructed through an application of Kendall's tau

cluster analysis,

Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma

The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome

Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes

Exercise increases AMPK (AMP-activated protein kinase) activity in human and rat adipocytes, but the underlying molecular mechanisms and functional consequences of this activation are not known. Since adrenaline (epinephrine) concentrations increase with exercise, in the present study we hypothesized that adrenaline activates AMPK in adipocytes. We show that a single bout of exercise increases AMPKα1 and α2 activities and ACC (acetyl-CoA carboxylase) Ser79 phosphorylation in rat adipocytes. Similarly to exercise, adrenaline treatment in vivo increased AMPK activities and ACC phosphorylation. Pre-treatment of rats with the β-blocker propranolol fully blocked exercise-induced AMPK activation. Increased AMPK activity with exercise and adrenaline treatment in vivo was accompanied by an increased AMP/ATP ratio. Adrenaline incubation of isolated adipocytes also increased the AMP/ATP ratio and AMPK activities, an effect blocked by propranolol. Adrenaline incubation increased lipolysis in isolated adipocytes, and Compound C, an AMPK inhibitor, attenuated this effect. Finally, a potential role for AMPK in the decreased adiposity associated with chronic exercise was suggested by marked increases in AMPKα1 and α2 activities in adipocytes from rats trained for 6 weeks. In conclusion, both acute and chronic exercise are significant regulators of AMPK activity in rat adipocytes. Our findings suggest that adrenaline plays a critical role in exercise-stimulated AMPKα1 and α2 activities in adipocytes, and that AMPK can function in the regulation of lipolysis