Clinical features distinguish cerebral amyloid angiopathy-associated convexity subarachnoid haemorrhage from suspected TIA

OBJECTIVE: To identity clinical features that distinguish between cerebral amyloid angiopathy (CAA)-associated convexity subarachnoid haemorrhage (cSAH) and suspected TIA. METHODS: We undertook a single-centre, retrospective case-control study. We identified cases [patients with cSAH presenting with transient focal neurological episodes (TFNE)] from radiological and clinical databases of patients assessed at the National Hospital for Neurology and Neurosurgery and UCLH Comprehensive Stroke Service. We identified age- and gender-matched controls at a 1:4 ratio from a database of consecutive suspected TIA clinic attendances at UCLH. We compared presenting symptoms and vascular risk factors between cases and controls. RESULTS: We included 19 patients with cSAH-associated TFNE and 76 matched controls with suspected TIA. Migratory (spreading) symptoms (32% vs. 3%, OR 17.3; p = 0.001), sensory disturbance (47% vs. 14%, OR 5.3; p = 0.003,) and recurrent stereotyped events (47% vs. 19%, OR 3.7; p = 0.02,) occurred more frequently in patients with cSAH compared to controls. Hypercholesterolaemia was less common in patients with cSAH (16% vs 53%, OR 0.17; p = 0.008). CONCLUSION: Simple clinical features could help distinguish cSAH-associated TFNE from suspected TIA, with relevance for investigation and management, including the use of antithrombotic drugs

The ‘SELection End points in Communities of bacTeria’ (SELECT) Method: A Novel Experimental Assay to Facilitate Risk Assessment of Selection for Antimicrobial Resistance in the Environment

This is the final version. Available on open access from NIEHS via the DOI in this recordBackground: Antimicrobial resistance (AMR) is one of the most significant health threats to society. A growing body of research demonstrates selection for AMR likely occurs at environmental concentrations of antibiotics. However, no standardized experimental approaches for determining selective concentrations of antimicrobials currently exist, preventing appropriate environmental and human health risk assessment of AMR. Objectives: We aimed to design a rapid, simple, and cost-effective novel experimental assay to determine selective effect concentrations of antibiotics and to generate the largest experimental data set of selective effect concentrations of antibiotics to date. Methods: Previously published methods and data were used to validate the assay, which determines the effect concentration based on reduction of bacterial community (wastewater) growth. Risk quotients for test antibiotics were generated to quantify risk. Results: The assay (SELection End points in Communities of bacTeria, or the SELECT method) was used to rapidly determine selective effect concentrations of antibiotics. These were in good agreement with quantitative polymerase chain reaction effect concentrations determined within the same experimental system. The SELECT method predicted no effect concentrations were minimally affected by changes in the assay temperature, growth media, or microbial community used as the inoculum. The predicted no effect concentrations for antibiotics tested ranged from 0.05μg/L for ciprofloxacin to 1,250μg/L for erythromycin. Discussion: The lack of evidence demonstrating environmental selection for AMR, and of associated human health risks, is a primary reason for the lack of action in the mitigation of release of antibiotics into the aquatic environment. We present a novel method that can reliably and rapidly fill this data gap to enable regulation and subsequent mitigation (where required) to lower the risk of selection for, and human exposure to, AMR in aquatic environments. In particular, ciprofloxacin and, to a lesser extent, azithromycin, cefotaxime, and trimethoprim all pose a significant risk for selection of AMR in the environment. https://doi.org/10.1289/EHP6635Biotechnology and Biological Sciences Research Council (BBSRC)AstraZeneca Collaborative Awards in Science and Engineering studentshipNatural Environment Research Council (NERC)Nuffield Foundatio

Does environmental exposure to pharmaceutical and personal care product residues result in the selection of antimicrobial‐resistant microorganisms, and is this important in terms of human health outcomes?

This is the final version. Available on open access from Wiley via the DOI in this record. Data Availability Statement: Data, associated metadata, and calculation tools are available from the corresponding author ([email protected]).The environment plays a critical role in the development, dissemination, and transmission of antimicrobial resistance (AMR). Pharmaceuticals and personal care products (PPCPs) enter the environment through direct application to the environment and through anthropogenic pollution. Although there is a growing body of evidence defining minimal selective concentrations (MSCs) of antibiotics and the role antibiotics play in horizontal gene transfer (HGT), there is limited evidence on the role of non-antibiotic PPCPs. Existing data show associations with the development of resistance or effects on bacterial growth rather than calculating selective endpoints. Research has focused on laboratory-based systems rather than in situ experiments, although PPCP concentrations found throughout wastewater, natural water, and soil environments are often within the range of laboratory-derived MSCs and at concentrations shown to promote HGT. Increased selection and HGT of AMR by PPCPs will result in an increase in total AMR abundance in the environment, increasing the risk of exposure and potential transmission of environmental AMR to humans. There is some evidence to suggest that humans can acquire resistance from environmental settings, with water environments being the most frequently studied. However, because this is currently limited, we recommend that more evidence be gathered to understand the risk the environment plays in regard to human health. In addition, we recommend that future research efforts focus on MSC-based experiments for non-antibiotic PPCPS, particularly in situ, and investigate the effect of PPCP mixtures on AM

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Competition for Cooperation: variability, benefits and heritability of relational wealth in hunter-gatherers

Many defining human characteristics including theory of mind, culture and language relate to our sociality, and facilitate the formation and maintenance of cooperative relationships. Therefore, deciphering the context in which our sociality evolved is invaluable in understanding what makes us unique as a species. Much work has emphasised group-level competition, such as warfare, in moulding human cooperation and sociality. However, competition and cooperation also occur within groups; and inter-individual differences in sociality have reported fitness implications in numerous non-human taxa. Here we investigate whether differential access to cooperation (relational wealth) is likely to lead to variation in fitness at the individual level among BaYaka hunter-gatherers. Using economic gift games we find that relational wealth: a) displays individual-level variation; b) provides advantages in buffering food risk, and is positively associated with body mass index (BMI) and female fertility; c) is partially heritable. These results highlight that individual-level processes may have been fundamental in the extension of human cooperation beyond small units of related individuals, and in shaping our sociality. Additionally, the findings offer insight in to trends related to human sociality found from research in other fields such as psychology and epidemiology

Altered patterns of cortical activation in ALS patients during attention and cognitive response inhibition tasks

Since amyotrophic lateral sclerosis (ALS) can be accompanied by executive dysfunction, it is hypothesised that ALS patients will have impaired performance on tests of cognitive inhibition. We predicted that ALS patients would show patterns of abnormal activation in extramotor regions when performing tests requiring the inhibition of prepotent responses (the Stroop effect) and the inhibition of prior negatively primed responses (the negative priming effect) when compared to healthy controls. Functional magnetic resonance imaging was used to measure activation during a sparse sequence block design paradigm investigating the Stroop and negative priming effects in 14 ALS patients and 8 healthy age- and IQ-matched controls. Behavioural measures of performance were collected. Both groups’ reaction times (RTs) reflected the Stroop effect during scanning. The ALS and control groups did not differ significantly for any of the behavioural measures but did show significant differences in cerebral activation during both tasks. The ALS group showed increased activation predominantly in the left middle temporal gyrus (BA 20/21), left superior temporal gyrus (BA 22) and left anterior cingulate gyrus (BA 32). Neither group’s RT data showed clear evidence of a negative priming effect. However the ALS group showed decreased activation, relative to controls, particularly in the left cingulate gyrus (BA 23/24), left precentral gyrus (BA 4/6) and left medial frontal gyrus (BA 6). Greater cerebral activation in the ALS group accompanying the performance of the Stroop effect and areas of decreased activation during the negative priming comparison suggest altered inhibitory processing in ALS, consistent with other evidence of executive dysfunction in ALS. The current findings require further exploration in a larger study