Limits to tDCS effects in language:failures to modulate word production in healthy participants with frontal or temporal tDCS

Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation widely used to modulate cognitive functions. Recent studies, however, suggests that effects are unreliable, small and often non-significant at least when stimulation is applied in a single session to healthy individuals. We examined the effects of frontal and temporal lobe anodal tDCS on naming and reading tasks and considered possible interactions with linguistic activation and selection mechanisms as well possible interactions with item difficulty and participant individual variability. Across four separate experiments (N, Exp 1A = 18; 1B = 20; 1C = 18; 2 = 17), we failed to find any difference between real and sham stimulation. Moreover, we found no evidence of significant effects limited to particular conditions (i.e., those requiring suppression of semantic interference), to a subset of participants or to longer RTs. Our findings sound a cautionary note on using tDCS as a means to modulate cognitive performance. Consistent effects of tDCS may be difficult to demonstrate in healthy participants in reading and naming tasks, and be limited to cases of pathological neurophysiology and/or to the use of learning paradigms

An adapted triage tool (ETAT) at Red Cross War Memorial Children’s Hospital Medical Emergency Unit, Cape Town: An evaluation

Objective. To evaluate the efficacy of an adapted Emergency Triage Assessment and Treatment (ETAT) tool at a children’s hospital. Design. A two-armed descriptive study. Setting. Red Cross War Memorial Children’s Hospital, Cape Town, South Africa. Methods. Triage data on 1 309 children from October 2007 and July 2009 were analysed. The number of children in each triage category (red (emergency), orange (urgent or priority) and green (non-urgent)) and their disposal were evaluated. Results. 1. The October 2007 series: 902 children aged 5 days - 15 years were evaluated. Their median age was 20 (interquartile range (IQR) 7 - 50) months, and 58.8% (n=530) were triaged green, 37.5% (n=338) orange and 3.8% (n=34) red. Over 90% of children in the green category were discharged (478/530), while 32.5% of children triaged orange (110/338) and 52.9% of children triaged red (18/34) were admitted. There was a significant increase in admission rate for each triage colour change from green through orange to red after adjustment for age category (risk ratio (RR) 2.6; 95% confidence interval (CI) 2.2 - 3.1). 2. The July 2009 cohort: 407 children with a median age of 22 months (IQR 7 - 53 months) were enrolled. Twelve children (2.9%) were triaged red, 187 (45.9%) orange and 208 (51.1%) green. A quarter (101/407) of the children triaged were admitted: 91.7% (11/12) from the red category and 36.9% (69/187) from the orange category were admitted, while 89.9% of children in the green category (187/208) were discharged. After adjusting for age category, admissions increased by more than 300% for every change in triage acuity (RR 3.2; 95% CI 2.5 - 4.1). Conclusions. The adapted ETAT process may serve as a reliable triage tool for busy paediatric medical emergency units in resource-constrained countries and could be evaluated further in community emergency settings

An adapted triage tool (ETAT) at Red Cross War Memorial Children’s Hospital Medical Emergency Unit, Cape Town: An evaluation

Objective. To evaluate the efficacy of an adapted Emergency Triage Assessment and Treatment (ETAT) tool at a children’s hospital. Design. A two-armed descriptive study. Setting. Red Cross War Memorial Children’s Hospital, Cape Town, South Africa. Methods. Triage data on 1 309 children from October 2007 and July 2009 were analysed. The number of children in each triage category (red (emergency), orange (urgent or priority) and green (non-urgent)) and their disposal were evaluated. Results. 1. The October 2007 series: 902 children aged 5 days - 15 years were evaluated. Their median age was 20 (interquartile range (IQR) 7 - 50) months, and 58.8% (n=530) were triaged green, 37.5% (n=338) orange and 3.8% (n=34) red. Over 90% of children in the green category were discharged (478/530), while 32.5% of children triaged orange (110/338) and 52.9% of children triaged red (18/34) were admitted. There was a significant increase in admission rate for each triage colour change from green through orange to red after adjustment for age category (risk ratio (RR) 2.6; 95% confidence interval (CI) 2.2 - 3.1). 2. The July 2009 cohort: 407 children with a median age of 22 months (IQR 7 - 53 months) were enrolled. Twelve children (2.9%) were triaged red, 187 (45.9%) orange and 208 (51.1%) green. A quarter (101/407) of the children triaged were admitted: 91.7% (11/12) from the red category and 36.9% (69/187) from the orange category were admitted, while 89.9% of children in the green category (187/208) were discharged. After adjusting for age category, admissions increased by more than 300% for every change in triage acuity (RR 3.2; 95% CI 2.5 - 4.1). Conclusions. The adapted ETAT process may serve as a reliable triage tool for busy paediatric medical emergency units in resource-constrained countries and could be evaluated further in community emergency settings

The natural capital of temporary rivers: characterising the value of dynamic aquatic-terrestrial habitats. Valuing Nature Natural Capital Synthesis Reports, VNP12

Temporary rivers naturally transition between flowing, pool and dry states, creating aquatic–terrestrial habitat mosaics that change in space and time. These dynamic habitats are common in the UK's cool, wet climate. Here, they take many forms, from headwater streams that may dominate networks in remote uplands, to winterbourne rivers crossing the chalk of south England. We examine published and unpublished sources to provide an evidence-informed characterisation of the natural assets in temporary rivers

The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium.

Tumour angiogenesis is a complex multistep process regulated by a number of angiogenic factors. One such factor, platelet-derived endothelial cell growth factor has recently been shown to be thymidine phosphorylase (TP). TP catalyses the reversible phosphorylation of thymidine to deoxyribose-1-phosphate and thymine. Although known to be generally elevated in tumours, the expression of this enzyme in breast carcinomas is unknown. Therefore, we used ribonuclease protection assays and immunohistochemistry to examine the expression of TP in 240 primary breast carcinomas. Nuclear and/or cytoplasmic TP expression was observed in the neoplastic tumour epithelium in 53% of tumours. Immunoreactivity was also often present in the stromal, inflammatory and endothelial cell elements. Although endothelial cell staining was usually focal, immunoreactivity was observed in 61% of tumours and was prominent at the tumour periphery, an area where tumour angiogenesis is most active. Tumour cell TP expression was significantly inversely correlated with grade (P = 0.05) and size (P = 0.003) but no association was observed with other tumour variables. These findings suggest that TP is important for remodelling the existing vasculature early in tumour development, consistent with its chemotactic non-mitogenic properties, and that additional angiogenic factors are more important for other angiogenic processes like endothelial cell proliferation. Relapse-free survival was higher in node-positive patients with elevated TP (P = 0.05) but not in other patient groups. This might be due to the potentiation of chemotherapeutic agents like methotrexate by TP. Therefore, this enzyme might be a prediction marker for response to chemotherapy

Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs