A wirelessly powered and controlled device for optical neural control of freely-behaving animals

Optogenetics, the ability to use light to activate and silence specific neuron types within neural networks in vivo and in vitro, is revolutionizing neuroscientists' capacity to understand how defined neural circuit elements contribute to normal and pathological brain functions. Typically, awake behaving experiments are conducted by inserting an optical fiber into the brain, tethered to a remote laser, or by utilizing an implanted light-emitting diode (LED), tethered to a remote power source. A fully wireless system would enable chronic or longitudinal experiments where long duration tethering is impractical, and would also support high-throughput experimentation. However, the high power requirements of light sources (LEDs, lasers), especially in the context of the extended illumination periods often desired in experiments, precludes battery-powered approaches from being widely applicable. We have developed a headborne device weighing 2 g capable of wirelessly receiving power using a resonant RF power link and storing the energy in an adaptive supercapacitor circuit, which can algorithmically control one or more headborne LEDs via a microcontroller. The device can deliver approximately 2 W of power to the LEDs in steady state, and 4.3 W in bursts. We also present an optional radio transceiver module (1 g) which, when added to the base headborne device, enables real-time updating of light delivery protocols; dozens of devices can be controlled simultaneously from one computer. We demonstrate use of the technology to wirelessly drive cortical control of movement in mice. These devices may serve as prototypes for clinical ultra-precise neural prosthetics that use light as the modality of biological control.National Institutes of Health (U.S.) (NIH Director’s New Innovator Award (DP2OD002002))National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1RC1MH088182)National Institutes of Health (U.S.) (Grant 1RC2DE020919)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Institutes of Health (U.S.) (Grant 1R43NS070453)National Science Foundation (U.S.) (CAREER award)National Science Foundation (U.S.) (NSF Grant DMS 1042134)National Science Foundation (U.S.) (NSF Grant DMS 0848804)National Science Foundation (U.S.) (NSF Grant EFRI 0835878)Benesse FoundationGoogle (Firm)Dr. Gerald Burnett and Marjorie BurnettUnited States. Dept. of Defense (CDMRP PTSD Program)Massachusetts Institute of TechnologyBrain & Behavior Research FoundationAlfred P. Sloan FoundationSociety for NeuroscienceMassachusetts Institute of Technology. Media LaboratoryMcGovern Institute for Brain Research at MITWallace H. Coulter Foundatio

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

Risk factors for ischaemic heart disease in a Cretan rural population: a twelve year follow-up study

<p>Abstract</p> <p>Background</p> <p>Crete has been of great epidemiological interest ever since the publication of the Seven Countries Study. In 1988 a well-defined area of rural Crete was studied, with only scarce signs of coronary heart disease (CHD) despite the unfavorable risk profile. The same population was re-examined twelve years later aiming to describe the trends of CHD risk factors over time and discuss some key points on the natural course of coronary heart disease in a rural population of Crete.</p> <p>Methods and Results</p> <p>We re-examined 200 subjects (80.7% of those still living in the area, 62.4 ± 17.0 years old). The prevalence of risk factors for CHD was high with 65.9% of men and 65.1% of women being hypertensive, 14.3% of men and 16.5% of women being diabetic, 44% of men being active smokers and more than 40% of both sexes having hyperlipidaemia. Accordingly, 77.5% of the population had a calculated Framingham Risk Score (FRS) ≥ 15%, significantly higher compared to baseline (p < 0.001). The overall occurrence rate for CHD events was calculated at 7.1 per 1000 person-years (95% confidence interval: 6.8–7.3).</p> <p>Conclusion</p> <p>The study confirms the unfavorable risk factor profile of a well defined rural population in Crete. Its actual effect on the observed incidence of coronary events in Cretans remains yet to be defined.</p

Evaluation of cell-free DNA approaches for multi-cancer early detection

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test

The concept of "compartment allergy": prilocaine injected into different skin layers

We herein present a patient with delayed-type allergic hypersensitivity against prilocaine leading to spreading eczematous dermatitis after subcutaneous injections for local anesthesia with prilocaine. Prilocaine allergy was proven by positive skin testing and subcutaneous provocation, whereas the evaluation of other local anesthetics - among them lidocaine, articaine and mepivacaine - did not exhibit any evidence for cross-reactivity

A historical perspective on the discovery of statins

Cholesterol is essential for the functioning of all human organs, but it is nevertheless the cause of coronary heart disease. Over the course of nearly a century of investigation, scientists have developed several lines of evidence that establish the causal connection between blood cholesterol, atherosclerosis, and coronary heart disease. Building on that knowledge, scientists and the pharmaceutical industry have successfully developed a remarkably effective class of drugs—the statins—that lower cholesterol levels in blood and reduce the frequency of heart attacks

DEPTH CAMERAS ON UAVs: A FIRST APPROACH

Accurate depth information retrieval of a scene is a field under investigation in the research areas of photogrammetry, computer vision and robotics. Various technologies, active, as well as passive, are used to serve this purpose such as laser scanning, photogrammetry and depth sensors, with the latter being a promising innovative approach for fast and accurate 3D object reconstruction using a broad variety of measuring principles including stereo vision, infrared light or laser beams. In this study we investigate the use of the newly designed Stereolab's ZED depth camera based on passive stereo depth calculation, mounted on an Unmanned Aerial Vehicle with an ad-hoc setup, specially designed for outdoor scene applications. Towards this direction, the results of its depth calculations and scene reconstruction generated by Simultaneous Localization and Mapping (SLAM) algorithms are compared and evaluated based on qualitative and quantitative criteria with respect to the ones derived by a typical Structure from Motion (SfM) and Multiple View Stereo (MVS) pipeline for a challenging cultural heritage application

Expression of Toll-like receptors (TLRs) in the lungs of an experimental sepsis mouse model

Background: Sepsis is a condition characterized by high mortality rates and often accompanied by multiple-organ dysfunction. During sepsis, respiratory system may be affected and possibly result in acute respiratory distress syndrome (ARDS). Toll-like receptors (TLRs), as a first line defense against invading pathogens, seem to be highly expressed in septic states. Therefore, expression of TLRs in the lungs of a sepsis animal model could indicate the involvement of the respiratory system and appear as a severity index of the clinical course. Materials and methods: A total of 72 C57BL/6J mice, aged 12–14 weeks, were studied. The animals were divided into 3 sepsis (S) groups (24h, 48h and 72h) and 3 control (C) groups (24h, 48h and 72h), each consisting of 12 mice. The S-groups were subjected to cecal ligation and puncture (CLP) while the C-groups had a sham operation performed. Blood samples were drawn from all groups. Total blood count analysis was performed along with the measurement of certain biochemical markers. Additionally, lung tissues were harvested and the expression of TLRs, namely TLR 2, TLR 3, TLR 4 and TLR 7 were evaluated by means of immunofluorescence (IF) and qRT-PCR (quantitative-Polymerase Chain Reaction). Statistical analysis was performed by using one-way ANOVA followed by student t-test. Results were considered statistically significant when p&lt;0.05. Results: WBCs and lymphocytes were decreased in all S-groups compared to the corresponding C-groups (p&lt;0.05), while RBCs showed a gradual decline in S-groups with the lowest levels appearing in the S72 group. Only, monocytes were higher in S-groups, especially between S48-C48 (p&lt;0.05) and S72-C72 (p&lt;0.05). Creatinine, IL-10 and IL-6 levels were significantly increased in the S-groups compared to the corresponding C-groups (S24 vs C24, S48 vs C48 and S72 vs C72, p&lt;0.05). IF showed that expression of TLRs 2, 3, 4 and 7 was increased in all S-groups compared to the time-adjusted C-groups (p&lt;0.05). Similarly, qRT-PCR revealed that expression of all TLRs was higher in all S-groups compared to their respective C-groups in both lungs and intestine (p&lt;0.05). Comparing lung and intestinal tissues from S-groups, TLRs 2 and 4 were found increased in the lung at 24, 48 and 72 hours (p&lt;0.05), whereas TLR 3 was higher in the intestine at all time points examined (p&lt;0.05). Finally, TLR 7 levels were significantly higher in the intestinal tissues at 24 hours (p&lt;0.0001), while lungs predominated at 48 hours (p&lt;0.0001). Conclusion: TLRs seem to be highly expressed in the lungs of septic mice, therefore suggesting a potential role in the pathogenesis of ARDS during sepsis. While more studies need to be conducted in order to completely understand the underlying mechanisms, TLRs may represent a promising target for establishing novel therapeutic strategies in the treatment of sepsis. © 2017 Bakopoulos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited