Wearable HD-DOT for investigating functional connectivity in the adult brain: A single subject, multi-session study

We applied a wearable 24-module high-density diffuse optical tomography (HD-DOT) system in a resting state (RS) paradigm repeatedly in one subject. Seed-based correlation maps show large field-of-view RS functional connectivity

Transcriptomic analysis of the zebrafish inner ear points to growth hormone mediated regeneration following acoustic trauma

Background: Unlike mammals, teleost fishes are capable of regenerating sensory inner ear hair cells that have been lost following acoustic or ototoxic trauma. Previous work indicated that immediately following sound exposure, zebrafish saccules exhibit significant hair cell loss that recovers to pre-treatment levels within 14 days. Following acoustic trauma in the zebrafish inner ear, we used microarray analysis to identify genes involved in inner ear repair following acoustic exposure. Additionally, we investigated the effect of growth hormone (GH) on cell proliferation in control zebrafish utricles and saccules, since GH was significantly up-regulated following acoustic trauma. Results: Microarray analysis, validated with the aid of quantitative real-time PCR, revealed several genes that were highly regulated during the process of regeneration in the zebrafish inner ear. Genes that had fold changes of \u3e = 1.4 and P values \u3c = 0.05 were considered significantly regulated and were used for subsequent analysis. Categories of biological function that were significantly regulated included cancer, cellular growth and proliferation, and inflammation. Of particular significance, a greater than 64-fold increase in growth hormone (gh1) transcripts occurred, peaking at 2 days post-sound exposure (dpse) and decreasing to approximately 5.5-fold by 4 dpse. Pathway Analysis software was used to reveal networks of regulated genes and showed how GH affected these networks. Subsequent experiments showed that intraperitoneal injection of salmon growth hormone significantly increased cell proliferation in the zebrafish inner ear. Many other gene transcripts were also differentially regulated, including heavy and light chain myosin transcripts, both of which were down-regulated following sound exposure, and major histocompatability class I and II genes, several of which were significantly regulated on 2 dpse. Conclusions: Transcripts for GH, MHC Class I and II genes, and heavy-and light-chain myosins, as well as many others genes, were differentially regulated in the zebrafish inner ear following overexposure to sound. GH injection increased cell proliferation in the inner ear of non-sound-exposed zebrafish, suggesting that GH could play an important role in sensory hair cell regeneration in the teleost ear

Phosphatidylinositol 3-kinase signaling in proliferating cells maintains an anti-apoptotic transcriptional program mediated by inhibition of FOXO and non-canonical activation of NFκB transcription factors

<p>Abstract</p> <p>Background</p> <p>Phosphatidylinositol (PI) 3-kinase is activated by a variety of growth factor receptors and the PI 3-kinase/Akt signaling pathway is a key regulator of cell proliferation and survival. The downstream targets of PI 3-kinase/Akt signaling include direct regulators of cell cycle progression and apoptosis as well as a number of transcription factors. Growth factor stimulation of quiescent cells leads to robust activation of PI 3-kinase, induction of immediate-early genes, and re-entry into the cell cycle. A lower level of PI 3-kinase signaling is also required for the proliferation and survival of cells maintained in the presence of growth factors, but the gene expression program controlled by PI 3-kinase signaling in proliferating cells has not been elucidated.</p> <p>Results</p> <p>We used microarray analyses to characterize the changes in gene expression resulting from inhibition of PI 3-kinase in proliferating cells. The genes regulated by inhibition of PI 3-kinase in proliferating cells were distinct from genes induced by growth factor stimulation of quiescent cells and highly enriched in genes that regulate programmed cell death. Computational analyses followed by chromatin immunoprecipitations demonstrated FOXO binding to both previously known and novel sites in promoter regions of approximately one-third of the up-regulated genes, consistent with activation of FOXO1 and FOXO3a in response to inhibition of PI 3-kinase. NFκB binding sites were similarly identified in promoter regions of over one-third of the down-regulated genes. RelB was constitutively bound to promoter regions in cells maintained in serum, however binding decreased following PI 3-kinase inhibition, indicating that PI 3-kinase signaling activates NFκB via the non-canonical pathway in proliferating cells. Approximately 70% of the genes targeted by FOXO and NFκB regulate cell proliferation and apoptosis, including several regulators of apoptosis that were not previously known to be targeted by these transcription factors.</p> <p>Conclusion</p> <p>PI 3-kinase signaling in proliferating cells regulates a novel transcriptional program that is highly enriched in genes that regulate apoptosis. At least one-third of these genes are regulated either by FOXO transcription factors, which are activated following PI 3-kinase inhibition, or by RelB, which is activated by PI 3-kinase via the non-canonical pathway in proliferating cells.</p

Wearable, Integrated EEG-fNIRS Technologies: A Review.

There has been considerable interest in applying electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) simultaneously for multimodal assessment of brain function. EEG-fNIRS can provide a comprehensive picture of brain electrical and hemodynamic function and has been applied across various fields of brain science. The development of wearable, mechanically and electrically integrated EEG-fNIRS technology is a critical next step in the evolution of this field. A suitable system design could significantly increase the data/image quality, the wearability, patient/subject comfort, and capability for long-term monitoring. Here, we present a concise, yet comprehensive, review of the progress that has been made toward achieving a wearable, integrated EEG-fNIRS system. Significant marks of progress include the development of both discrete component-based and microchip-based EEG-fNIRS technologies; modular systems; miniaturized, lightweight form factors; wireless capabilities; and shared analogue-to-digital converter (ADC) architecture between fNIRS and EEG data acquisitions. In describing the attributes, advantages, and disadvantages of current technologies, this review aims to provide a roadmap toward the next generation of wearable, integrated EEG-fNIRS systems

Learning to prescribe - pharmacists' experiences of supplementary prescribing training in England

Background: The introduction of non-medical prescribing for professions such as pharmacy and nursing in recent years offers additional responsibilities and opportunities but attendant training issues. In the UK and in contrast to some international models, becoming a non-medical prescriber involves the completion of an accredited training course offered by many higher education institutions, where the skills and knowledge necessary for prescribing are learnt. Aims: to explore pharmacists' perceptions and experiences of learning to prescribe on supplementary prescribing (SP) courses, particularly in relation to inter-professional learning, course content and subsequent use of prescribing in practice. Methods: A postal questionnaire survey was sent to all 808 SP registered pharmacists in England in April 2007, exploring demographic, training, prescribing, safety culture and general perceptions of SP. Results: After one follow-up, 411 (51%) of pharmacists responded. 82% agreed SP training was useful, 58% agreed courses provided appropriate knowledge and 62% agreed that the necessary prescribing skills were gained. Clinical examination, consultation skills training and practical experience with doctors were valued highly; pharmacology training and some aspects of course delivery were criticised. Mixed views on inter-professional learning were reported – insights into other professions being valued but knowledge and skills differences considered problematic. 67% believed SP and recent independent prescribing (IP) should be taught together, with more diagnostic training wanted; few pharmacists trained in IP, but many were training or intending to train. There was no association between pharmacists' attitudes towards prescribing training and when they undertook training between 2004 and 2007 but earlier cohorts were more likely to be using supplementary prescribing in practice. Conclusion: Pharmacists appeared to value their SP training and suggested improvements that could inform future courses. The benefits of inter-professional learning, however, may conflict with providing professionspecific training. SP training may be perceived to be an instrumental 'stepping stone' in pharmacists' professional project of gaining full IP status

Transcriptomic Analysis of Age-Associated Periventricular Lesions Reveals Dysregulation of the Immune Response.

White matter lesions (WML) are a common feature of the ageing brain associated with cognitive impairment. The gene expression profiles of periventricular lesions (PVL, n = 7) and radiologically-normal-appearing (control) periventricular white matter cases (n = 11) obtained from the Cognitive Function and Ageing Study (CFAS) neuropathology cohort were interrogated using microarray analysis and NanoString to identify novel mechanisms potentially underlying their formation. Histological characterisation of control white matter cases identified a subgroup (n = 4) which contained high levels of MHC-II immunoreactive microglia, and were classified as "pre-lesional." Microarray analysis identified 2256 significantly differentially-expressed genes (p ≤ 0.05, FC ≥ 1.2) in PVL compared to non-lesional control white matter (1378 upregulated and 878 downregulated); 2649 significantly differentially-expressed genes in "pre-lesional" cases compared to PVL (1390 upregulated and 1259 downregulated); and 2398 significantly differentially-expressed genes in "pre-lesional" versus non-lesional control cases (1527 upregulated and 871 downregulated). Whilst histological evaluation of a single marker (MHC-II) implicates immune-activated microglia in lesion pathology, transcriptomic analysis indicates significant downregulation of a number of activated microglial markers and suggests established PVL are part of a continuous spectrum of white matter injury. The gene expression profile of "pre-lesional" periventricular white matter suggests upregulation of several signalling pathways may be a neuroprotective response to prevent the pathogenesis of PVL

L-plastin is essential for alveolar macrophage production and control of pulmonary pneumococcal infection

We report that mice deficient for the hematopoietic-specific, actin-bundling protein L-plastin (LPL) succumb rapidly to intratracheal pneumococcal infection. The increased susceptibility of LPL(−/−) mice to pulmonary pneumococcal challenge correlated with reduced numbers of alveolar macrophages, consistent with a critical role for this cell type in the immediate response to pneumococcal infection. LPL(−/−) mice demonstrated a very early clearance defect, with an almost 10-fold-higher bacterial burden in the bronchoalveolar lavage fluid 3 h following infection. Clearance of pneumococci from the alveolar space in LPL(−/−) mice was defective compared to that in Rag1(−/−) mice, which lack all B and T lymphocytes, indicating that innate immunity is defective in LPL(−/−) mice. We did not identify defects in neutrophil or monocyte recruitment or in the production of inflammatory cytokines or chemokines that would explain the early clearance defect. However, efficient alveolar macrophage regeneration following irradiation required LPL. We thus identify LPL as being key to alveolar macrophage development and essential to an effective antipneumococcal response. Further analysis of LPL(−/−) mice will illuminate critical regulators of the generation of alveolar macrophages and, thus, effective pulmonary innate immunity

In vivo transplantation of enteric neural crest cells into mouse gut; Engraftment, functional integration and long-term safety

Objectives: Enteric neuropathies are severe gastrointestinal disorders with unsatisfactory outcomes. We aimed to investigate the potential of enteric neural stem cell therapy approaches for such disorders by transplanting mouse enteric neural crest cells (ENCCs) into ganglionic and aganglionic mouse gut in vivo and analysing functional integration and long-term safety. Design: Neurospheres gene