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Background: Alzheimer's disease (AD) is a neurodegenerative disease without known cure. However, early medical treatment can help control its progression and postpone intellectual decay. Since AD is preceded by a period of cognitive deterioration, the effective assessment of cognitive capabilities is crucial to develop reliable screening procedures. For this purpose, cognitive tests are extensively used to evaluate cognitive areas such as language, attention, or memory. Methods: In this work, we analyzed the potential of a visual dynamics evaluation, the rapid serial visual presentation task (RSVP), for the detection of cognitive impairment in AD. We compared this evaluation with two of the most extended brief cognitive tests applied in Spain: the Clock-drawing test (CDT) and the Phototest. For this purpose, we assessed a group of patients (mild AD and mild cognitive impairment) and controls, and we evaluated the ability of the three tests for the discrimination of the two groups. Results: The preliminary results obtained suggest the RSVP performance is statistically higher for the controls than for the patients (p-value = 0.013). Furthermore, we obtained promising classification results for this test (mean accuracy of 0.91 with 95% confidence interval 0.72, 0.97). Conclusions: Since the RSVP is a computerized, auto-scored, and potentially self-administered brief test, it could contribute to speeding-up cognitive impairment screening and to reducing the associated costs. Furthermore, this evaluation could be combined with other tests to augment the efficiency of cognitive impairment screening protocols and to potentially monitor patients under medical treatment. [ABSTRACT FROM AUTHOR]

A novel pressure transducer concept is introduced in which external pressure variations induce changes in the volume of a trapped microbubble ( \mu \textB ) in an electrolyte solution. These volumetric changes are monitored by electrochemical impedance-based measurements and may be used for pressure tracking applications. Microbubbles are nucleated on-demand by electrolysis within a confinement chamber with high precision (measured size RSD $\sim 1$ %). This pressure transducer concept was developed specifically for operation in liquid environments and features biocompatible construction, small footprint (<0.1 mm2), and low power consumption (<1 nW). This combination of features is ideal for in vivo pressure monitoring applications. [2015-0203] [ABSTRACT FROM PUBLISHER]

To investigate the mechanical interactions between the implanted cortical multielectrode probes and brain tissue, a Parylene C-based electrochemical-microelectromechanical systems force sensor array was developed. The array consists of seven linearly distributed sensor units arranged along the length of a flexible Parylene C microchannel. The seven sensor units are formed by eight fluidically coupled and adjacent platinum electrode pairs enclosed within the microchannel. Deformation of the top surface of the mechanically compliant microchannel changes the volumetric conduction path between the pairs of sensing electrodes, and therefore, the measured electrochemical impedance, which is proportional to the magnitude of the contacting force. Each sensor unit demonstrated a linear response from 0 to 60 mN with a sensitivity of 0.13 ± 0.01 percentage change in impedance/ \mu \textN (%/ \mu \textN ; mean ± SE, n = 6 ). The sensor arrays were mounted onto a ceramic intracortical probe and inserted into the tissue phantoms to verify in situ functionality and assess interfacial probe mechanics. Probe surface force distribution was measured under various insertion speeds and the results indicated that interfacial forces are distributed nonuniformly along the probe shaft length, concentrating within the first 1 mm of the advancing probe tip. Faster insertion speeds were also found to decrease the magnitude of the interfacial forces, suggesting that the tissue strain during cortical implantation may be minimized through appropriate selection of the insertion speed.[2014-0320] [ABSTRACT FROM PUBLISHER]

Abstract: Primary retinal cultures constitute valuable tools not only for basic research on retinal cell development and physiology, but also for the identification of factors or drugs that promote cell survival and differentiation. In order to take full advantage of the benefits of this system it is imperative to develop efficient and reliable techniques for the manipulation of gene expression. However, achieving appropriate transfection efficiencies in these cultures has remained challenging. The purpose of this work was to develop and optimize a technique that would allow the transfection of chick retinal cells with high efficiency and reproducibility for multiple applications. We developed an ex vivo electroporation method applied to dissociated retinal cell cultures that offers a significant improvement over other currently available transfection techniques, increasing efficiency by five-fold. In this method, eyes were enucleated, devoid of RPE, and electroporated with GFP-encoding plasmids using custom-made electrodes. Electroporated retinas were then dissociated into single cells and plated in low density conditions, to be analyzed after 4 days of incubation. Parameters such as voltage and number of electric pulses, as well as plasmid concentration and developmental stage of the animal were optimized for efficiency. The characteristics of the cultures were assessed by morphology and immunocytochemistry, and cell viability was determined by ethidium homodimer staining. Cell imaging and counting was performed using an automated high-throughput system. This procedure resulted in transfection efficiencies in the order of 22–25% of cultured cells, encompassing both photoreceptors and non-photoreceptor neurons, and without affecting normal cell survival and differentiation. Finally, the feasibility of the technique for cell-autonomous studies of gene function in a biologically relevant context was tested by carrying out gain and loss-of-function experiments for the transcription factor PAX6. Electroporation of a plasmid construct expressing PAX6 resulted in a marked upregulation in the expression levels of this protein that could be measured in the whole culture as well as cell-intrinsically. This was accompanied by a significant decrease in the percentage of cells differentiating as photoreceptors among the transfected population. Conversely, electroporation of an RNAi construct targeting PAX6 resulted in a significant decrease in the levels of this protein, with a concomitant increase in the proportion of photoreceptors. Taken together these results provide strong proof-of-principle of the suitability of this technique for genetic studies in retinal cultures. The combination of the high transfection efficiency obtained by this method with automated high-throughput cell analysis supplies the scientific community with a powerful system for performing functional studies in a cell-autonomous manner. [Copyright &y& Elsevier]

We report on the use of electrochemical impedance (EI) as the basis for force transduction in Parylene-based microdevices. Electrolyte-filled microstructures were realized for extremely sensitive contact-force detection (10 mN range, \pm0.023 mN resolution) enabled by EI-based transduction and are a promising platform for next-generation biomedical sensing technology. The design, fabrication, and characterization of Parylene-based electrochemical-MEMS (EC-MEMS) devices capable of microNewton contact-mode force measurement are presented and discussed.\hfill[2011-0040] [ABSTRACT FROM AUTHOR]

We report the design, fabrication, and characterization of electrochemical microelectromechanical systems (EC-MEMS) devices featuring encapsulated fluid as the basis for transduction. Parylene microstructures, including discrete chambers (square or circular geometry), are utilized as physical transducers for electrochemically mediated liquid impedance transduction of physical phenomenon such as contact and force. Parylene-based EC-MEMS technologies uniquely leverage advantages in size (<500\ \mu\m diameter), packaging (no hermetic packaging necessary), power (nanowatts to microwatts), and flexibility to address the physical sensing requirements of in vivo applications. Robust EC impedance (EI) sensor responses (up to 20% from base-line) and discrimination of 200-nm chamber deflections were possible using the EI transduction technique. Additional transducer configurations enabling electrolysis-based out-of-plane actuation and biomimetic mechanotransduction in microfluidic channels are also presented. \hfill[2010-0157] [ABSTRACT FROM AUTHOR]

We developed a constituent quark-diquark model for the nucleon and its resonances using a harmonic oscillator potential for the interaction. The effects due to relativistic kinetic energy correction are studied. Finally, charge form factor of the model is calculated and compared with experimental data. [ABSTRACT FROM AUTHOR]

We identified a mechanism whereby retina regeneration in the embryonic chick can be induced by the contribution of stem/ progenitor cells. We show that bone morphogenetic protein (BMP) signaling is sufficient and necessary to induce retina regeneration and that its action can be divided into two phases. By 3 days after postretinectomy (d PR), the BMP pathway directs proliferation and regeneration through the activation of Smad (canonical BMP pathway) and the up-regulation of FGF signaling by the MAPK path- way. By 7d PR. it induces apoptosis by activating p38 (a noncanonical BMP pathway) and down-regulating FGF signaling (by both MAPK and AKT pathways). Apoptosis at this later stage can be prevented, and BMP-induced regeneration can be further induced by inhibition of p38. These results unravel a mechanism for stem/progenitor cell-mediated retina regeneration, where BMP activation establishes a cross-talk with the FGF pathway and selectively activates the canonical and noncanonical BMP pathways. Retina stem/progenitor cells exist in other species, including humans. Thus, our findings provide insights on how retinal stem cells can be activated for possible regenerative therapies. [ABSTRACT FROM AUTHOR]

Bulk RNA sequencing of a tissue captures the gene expression profile from all cell types combined. Single-cell RNA sequencing identifies discrete cell-signatures based on transcriptomic identities. Six adult human corneas were processed for single-cell RNAseq and 16 cell clusters were bioinformatically identified. Based on their transcriptomic signatures and RNAscope results using representative cluster marker genes on human cornea cross-sections, these clusters were confirmed to be stromal keratocytes, endothelium, several subtypes of corneal epithelium, conjunctival epithelium, and supportive cells in the limbal stem cell niche. The complexity of the epithelial cell layer was captured by eight distinct corneal clusters and three conjunctival clusters. These were further characterized by enriched biological pathways and molecular characteristics which revealed novel groupings related to development, function, and location within the epithelial layer. Moreover, epithelial subtypes were found to reflect their initial generation in the limbal region, differentiation, and migration through to mature epithelial cells. The single-cell map of the human cornea deepens the knowledge of the cellular subsets of the cornea on a whole genome transcriptional level. This information can be applied to better understand normal corneal biology, serve as a reference to understand corneal disease pathology, and provide potential insights into therapeutic approaches. [ABSTRACT FROM AUTHOR]

We present the first electrochemical actuator with Parylene bellows for large-deflection operation. The bellows diaphragm was fabricated using a polyethylene-glycol-based sacrificial molding technique followed by coating in Parylene C. Bellows were mechanically characterized and integrated with a pair of interdigitated electrodes to form an electrochemical actuator that is suitable for low-power pumping of fluids. Pump performance (gas generation rate and pump efficiency) was optimized through a careful examination of geometrical factors. Overall, a maximum pump efficiency of 90% was achieved in the case of electroplated electrodes, and a deflection of over 1.5 mm was demonstrated. Real-time wireless operation was achieved. The complete fabrication process and the materials used in this actuator are bio-compatible, which makes it suitable for biological and medical applications. [ABSTRACT FROM AUTHOR]

In a cold greenhouse the vegetative production of Bromus berteroanus Colla was studied under different actual simulated pluviometric regimes of the dry land areas of the Metropolitan Region, Chile. Three levels of total rainfall were used, corresponding to dry, normal, and rainy years, with each year having early, normal, and late distributions. Rainfall levels for each treatment were applied, according to a real calendar time interval between rainfalls, beginning with the first effective rainfall. Phenological development and vegetative phytomass were registered, including shoots per pot, and dry matter of shoots, leaves and roots. In all the types of years studied, B. berteroanus had a determined development with a marked separation of the phenological phases, the vegetative stage was longer than the reproductive one, and both stages were more extended under the greatest rainfall when the distribution was not considered. The phytomass production was affected by the total quantity as well as the distribution of rainfall. In dry years, the greatest total phytomass occurred under early rainfall distribution (9.2 g DM/pot), on the other hand, in normal or rainy years, the greatest production was obtained under late rainfall distributions, 13.7 and 23.1 g DM/pot, respectively. [ABSTRACT FROM AUTHOR]

Complement components have been implicated in a wide variety of functions including neurogenesis, proliferation, cell migration, differentiation, cancer, and more recently early development and regeneration. Following our initial observations indicating that C3a/C3aR signaling induces chick retina regeneration, we analyzed its role in chick eye morphogenesis. During eye development, the optic vesicle (OV) invaginates to generate a bilayer optic cup (OC) that gives rise to the retinal pigmented epithelium (RPE) and neural retina. We show by immunofluorescence staining that C3 and the receptor for C3a (the cleaved and active form of C3), C3aR, are present in chick embryos during eye morphogenesis in the OV and OC. Interestingly, C3aR is mainly localized in the nuclear compartment at the OC stage. Loss of function studies at the OV stage using morpholinos or a blocking antibody targeting the C3aR (anti-C3aR Ab), causes eye defects such as microphthalmia and defects in the ventral portion of the eye that result in coloboma. Such defects were not observed when C3aR was disrupted at the OC stage. Histological analysis demonstrated that microphthalmic eyes were unable to generate a normal optic stalk or a closed OC. The dorsal/ventral patterning defects were accompanied by an expansion of the ventral markers Pax2, cVax and retinoic acid synthesizing enzyme raldh -3 ( aldh1a3 ) domains, an absence of the dorsal expression of Tbx5 and raldh-1 ( aldh1a1 ) and a re-specification of the ventral RPE to neuroepithelium. In addition, the eyes showed overall decreased expression of Gli1 and a change in distribution of nuclear β-catenin, suggesting that Shh and Wnt pathways have been affected. Finally, we observed prominent cell death along with a decrease in proliferating cells, indicating that both processes contribute to the microphthalmic phenotype. Together our results show that C3aR is necessary for the proper morphogenesis of the OC. This is the first report implicating C3aR in eye development, revealing an unsuspected hitherto regulator for proper chick eye morphogenesis. [ABSTRACT FROM AUTHOR]

The derivation and maintenance of human pluripotent stem cells (hPSCs) in stable naïve pluripotent states has a wide impact in human developmental biology. However, hPSCs are unstable in classical naïve mouse embryonic stem cell (ESC) WNT and MEK/ERK signal inhibition (2i) culture. We show that a broad repertoire of conventional hESC and transgene-independent human induced pluripotent stem cell (hiPSC) lines could be reverted to stable human preimplantation inner cellmass (ICM)-like naïve states with only WNT, MEK/ERK, and tankyrase inhibition (LIF-3i). LIF-3i-reverted hPSCs retained normal karyotypes and genomic imprints, and attained defining mouse ESC-like functional features, including high clonal self-renewal, independence from MEK/ERK signaling, dependence on JAK/ STAT3 and BMP4 signaling, and naïve-specific transcriptional and epigenetic configurations. Tankyrase inhibition promoted a stable acquisition of a human preimplantation ICM-like ground state via modulation of WNT signaling, and was most efficacious in efficiently reprogrammed conventional hiPSCs. Importantly, naïve reversion of a broad repertoire of conventional hiPSCs reduced lineage-primed gene expression and significantly improved their multilineage differentiation capacities. Stable naïve hPSCs with reduced genetic variability and improved functional pluripotency will have great utility in regenerative medicine and human disease modeling. [ABSTRACT FROM AUTHOR]

Abstract: Novel flexible parylene-based high-density electrode arrays have been developed for functional electrical stimulation in retinal and spinal cord prosthetics. These arrays are microfabricated according to a single-metal-layer process and a revolutionary dual-metal-layer process that promises to meet the needs of extremely high-density stimulation applications. While in many cases thin-film platinum electrodes in parylene C would be sufficient, high surface-area platinum electroplating has been shown to extend the lifetime of stimulated electrodes to more than 430 million pulses without failing. Iridium electrode arrays with higher charge delivery capacity have also been fabricated using a new high-temperature stabilized parylene variant, parylene HT. In addition, a new heat molding process has been implemented to conform electrode arrays to approximate the curvature of canine retinas, and a chronic implantation study of the mechanical effects of parylene-based electrode arrays on the retina over a 6-month follow-up period has provided excellent results. Retinal stimulation from these parylene-based electrode arrays in an isolated tiger salamander preparation was shown to be comparable to light stimulation in terms of generation of action potentials in the inner retina. Finally, electrode arrays have also been implanted and tested on the spinal cords of murine models, with the ultimate goal of facilitation of locomotion after spinal cord injury; these arrays provide a higher density and better spatial control of stimulation and recording than is typically possible using traditional fine-wire electrodes. Spinal cord stimulation typically elicited three muscle responses, an early (direct), a middle (monosynaptic), and a late (polysynaptic) response, classified based on latency after stimulation. Stimulation at different rostrocaudal levels of the cord yielded markedly different muscle responses, highlighting the need for such high-density arrays. [Copyright &y& Elsevier]

Among 397 homeless participants studied, the overall West Nile virus (WNV) seroprevalence was 6.8%. Risk factors for WNV infection included being homeless >1 year, spending >6 hours outside daily, regularly taking mosquito precautions, and current marijuana use. Public health interventions need to be directed toward this high-risk population. [ABSTRACT FROM AUTHOR]