Computerized spatial delayed recognition span task: a specific tool to assess visuospatial working memory

A new tablet device version (IOS platform) of the Spatial Delayed Recognition Span Task (SDRST) was developed with the aim of investigating visuospatial Working Memory (WM) abilities based on touchscreen technology. This new WM testing application will be available to download for free in Apple Store app (“SDRST app”). In order to verify the feasibility of this computer-based task, we conducted three experiments with different manipulations and groups of participants. We were interested in investigating if (1) the SDRST is sensitive enough to tap into cognitive differences brought by aging and dementia; (2) different experimental manipulations work successfully; (3) cortical brain activations seen in other WM tasks are also demonstrated here; and (4) non-human primates are able to answer the task. Performance (scores and response time) was better for young than older adults and higher for the latter when compared to Alzheimer’s disease (AD) patients. All groups performed better with facial stimuli than with images of scenes and with emotional than with neutral stimuli. Electrophysiology data showed activation on prefrontal and frontal areas of scalp, theta band activity on the midline area, and gamma activity in left temporal area. There are all scalp regions known to be related to attention and WM. Besides those data, our sample of adult captive capuchin monkeys (Sapajus libidinosus) answered the task above chance level. Taken together, these results corroborate the reliability of this new computer-based SDRST as a measure of visuospatial WM in clinical and non-clinical populations as well as in non-human primates. Its tablet app allows the task to be administered in a wide range of settings, including hospitals, homes, schools, laboratories, universities, and research institutions

Age-Related Differences in Cortical Activity during a Visuo-Spatial Working Memory Task with Facial Stimuli

Emotion, importantly displayed by facial expressions, is one of the most significant memory modulators. The interaction between memory and the different emotional valences change across lifespan, while young adults (YA) are expected to better recall negative events (Negativity Bias Hypothesis), older adults (OA) tend to focus on positive stimuli (Positivity Effect Hypothesis). This research work aims at verifying whether cortical electrical activity of these two age groups would also be differently influenced by emotional valences in a visuo-spatial working memory task. 27 YA (13 males) and 25 OA (14 males), all healthy volunteers, underwent electroencephalographic recordings (21 scalp electrodes montage), while performing the Spatial Delayed Recognition Span Task using a touch screen with different stimuli categories: neutral, positive and negative faces and geometric pictures. YA obtained higher scores than OA, and showed higher activation of theta and alpha bands in the frontal and midline regions, besides a more evident right-hemispheric asymmetry on alpha band when compared to OA. For both age groups, performance in the task was worse for positive faces than to negative and to neutral faces. Facial stimuli induced a better performance and higher alpha activation on the pre-frontal region for YA, and on the midline, occipital and left temporal regions for OA when compared to geometric figures. The superior performance of YA was expected due to the natural cognitive deficits connected to ageing, as was a better performance with facial stimuli due to the evolutionary importance of faces. These results were related to cortical activity on areas of importance for action-planning, decision making and sustained attention. Taken together, they are in accordance with the Negativity Bias but do not support the Positivity Effect. The methodology used was able to identify age-related differences in cortical activity during emotional mnemonic processing and may be interesting to future investigations

Echocardiographic assessment of aortic stenosis: a practical guideline from the British Society of E.

The guideline provides a practical step-by-step guide in order to facilitate high quality echocardiographic studies of patients with aortic stenosis. In addition, it addresses commonly encountered yet challenging clinical scenarios and covers the use of advanced echocardiographic techniques, including TOE and dobutamine stress echocardiography in the assessment of aortic stenosis

Transthoracic Echocardiographic Assessment of the Heart in Pregnancy-a position statement on behalf of the British Society of Echocardiography and the United Kingdom Maternal Cardiology Society.

Pregnancy is a dynamic process associated with profound hormonally mediated haemodynamic changes which result in structural and functional adaptations in the cardiovascular system. An understanding of the myocardial adaptations is important for echocardiographers and clinicians undertaking or interpreting echocardiograms on pregnant and post-partum women. This guideline, on behalf of the British Society of Echocardiography and United Kingdom Maternal Cardiology Society, reviews the expected echocardiographic findings in normal pregnancy and in different cardiac disease states, as well as echocardiographic signs of decompensation. It aims to lay out a structure for echocardiographic scanning and surveillance during and after pregnancy as well as suggesting practical advice on scanning pregnant women

Protease Activated Receptor Signaling Is Required for African Trypanosome Traversal of Human Brain Microvascular Endothelial Cells

Human African trypanosomiasis, or sleeping sickness, occurs when single-cell trypanosome protozoan parasites spread from the blood to brain over the blood-brain barrier (BBB). This barrier is composed of brain microvascular endothelial cells (BMECs) especially designed to keep pathogens out. Safe drugs for treating sleeping sickness are lacking and alternative treatments are urgently required. Using our human BMEC BBB model, we previously found that a parasite protease, brucipain, induced calcium activation signals that allowed this barrier to open up to parasite crossing. Because human BMECs express protease-activated receptors (PARs) that trigger calcium signals in BMECs, we hypothesized a functional link between parasite brucipain and BMEC PARs. Utilizing RNA interference to block the production of one type of PAR called PAR-2, we hindered the ability of trypanosomes to both open up and cross human BMECs. Using gene-profiling methods to interrogate candidate BMEC pathways specifically triggered by brucipain, several pathways that potentially link brain inflammatory processes were identified, a finding congruent with the known role of PAR-2 as a mediator of inflammation. Overall, our data support a role for brucipain and BMEC PARs in trypanosome BBB transmigration, and as potential triggers for brain inflammation associated with the disease

Phylogenetic Analysis of the Neks Reveals Early Diversification of Ciliary-Cell Cycle Kinases

NIMA-related kinases (Neks) have been studied in diverse eukaryotes, including the fungus Aspergillus and the ciliate Tetrahymena. In the former, a single Nek plays an essential role in cell cycle regulation; in the latter, which has more than 30 Neks in its genome, multiple Neks regulate ciliary length. Mammalian genomes encode an intermediate number of Neks, several of which are reported to play roles in cell cycle regulation and/or localize to centrosomes. Previously, we reported that organisms with cilia typically have more Neks than organisms without cilia, but were unable to establish the evolutionary history of the gene family

Integrative approach for differentially overexpressed genes in gastric cancer by combining large-scale gene expression profiling and network analysis

Gene expression profiling is a valuable tool for identifying differentially expressed genes in studies of disease subtype and patient outcome for various cancers. However, it remains difficult to assign biological significance to the vast number of genes. There is an increasing awareness of gene expression profile as an important part of the contextual molecular network at play in complex biological processes such as cancer initiation and progression. This study analysed the transcriptional profiles commonly activated at different stages of gastric cancers using an integrated approach combining gene expression profiling of 222 human tissues and gene regulatory dynamic mapping. We focused on an inferred core network with CDKN1A (p21WAF1/CIP1) as the hub, and extracted seven candidates for gastric carcinogenesis (MMP7, SPARC, SOD2, INHBA, IGFBP7, NEK6, LUM). They were classified into two groups based on the correlation between expression level and stage. The seven genes were commonly activated and their expression levels tended to increase as disease progressed. NEK6 and INHBA are particularly promising candidate genes overexpressed at the protein level, as confirmed by immunohistochemistry and western blotting. This integrated approach could help to identify candidate players in gastric carcinogenesis and progression. These genes are potential markers of gastric cancer regardless of stage

Initiation of human colon cancer cell proliferation by trypsin acting at protease-activated receptor-2

The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin. We investigated the expression of PAR-2 and the role of trypsin in cell proliferation in human colon cancer cell lines. A total of 10 cell lines were tested for expression of PAR-2 mRNA by Northern blot and RT-PCR. PAR-2 protein was detected by immunofluorescence. Trypsin and the peptide agonist SLIGKV (AP2) were tested for their ability to induce calcium mobilization and to promote cell proliferation on serum-deprived cells. PAR-2 mRNA was detected by Northern blot analysis in 6 out of 10 cell lines [HT-29, Cl.19A, Caco-2, SW480, HCT-8 and T84]. Other cell lines expressed low levels of transcripts, which were detected only by RT-PCR. Further results were obtained with HT-29 cells: (1) PAR-2 protein is expressed at the cell surface; (2) an increase in intracellular calcium concentration was observed upon trypsin (1–100 nM) or AP2 (10–100 μM) challenges; (3) cells grown in serum-deprived media supplemented with trypsin (0.1–1 nM) or AP2 (1–300 μM) exhibited important mitogenic responses (3-fold increase of cell number). Proliferative effects of trypsin or AP2 were also observed in other cell lines expressing PAR-2. These data show that subnanomolar concentrations of trypsin, acting at PAR-2, promoted the proliferation of human colon cancer cells. The results of this study indicate that trypsin could be considered as a growth factor and unravel a new mechanism whereby serine proteases control colon tumours. © 2001 Cancer Research Campaign http://www.bjcancer.co