Electrophysiological pattern of involuntary limb movements in the restless legs syndrome

Patients with restless legs syndrome (RLS) suffer from involuntary limb movements during the day. We studied these leg movements in 18 idiopathic (n = 8) and uremic (n = 10) patients at rest. Electromyographically measured muscle contractions were preceded by sensory discomfort in all patients. The mean duration of the contractions ranged between 0.67 and 5.71 s with a mean frequency of 244 epochs of muscle activity per hour. Seven of 18 patients showed a constant order of recruitment with propagation of muscle activity up or down spinal segments (L3 to S1 and vice versa). No difference in electrophysiologically recorded patterns was observed between patients with idiopathic and uremic RLS. We suggest a brainstem disinhibition phenomenon as the pathological mechanism that activates a spinal generator. The spinal origin of the involuntary limb movements in patients with RLS is confirmed by the long duration of jerks, the recruitment characteristics, and the periodicity of the jerks. No jerk could be elicited by sensory reflexes. © 1996 John Wiley & Sons, Inc.     

Surface NMR using quantum sensors in diamond

NMR is a noninvasive, molecular-level spectroscopic technique widely used for chemical characterization. However, it lacks the sensitivity to probe the small number of spins at surfaces and interfaces. Here, we use nitrogen vacancy (NV) centers in diamond as quantum sensors to optically detect NMR signals from chemically modified thin films. To demonstrate the method’s capabilities, aluminum oxide layers, common supports in catalysis and materials science, are prepared by atomic layer deposition and are subsequently functionalized by phosphonate chemistry to form self-assembled monolayers. The surface NV-NMR technique detects spatially resolved NMR signals from the monolayer, indicates chemical binding, and quantifies molecular coverage. In addition, it can monitor in real time the formation kinetics at the solid–liquid interface. With our approach, we show that NV quantum sensors are a surface-sensitive NMR tool with femtomole sensitivity for in situ analysis in catalysis, materials, and biological research.

The characterization of surface processes at the molecular level is essential for understanding fundamental processes in industrial catalysis, energy conversion, electronic circuits, targeted drug delivery, and biosensing (1). However, many analytical techniques used in surface science are inaccessible under ambient or chemically relevant conditions. Therefore, it remains challenging to perform chemical analysis under the conditions in which these processes occur (2, 3). Commonly used surface sensitive methods, such as X-ray photoelectron spectroscopy (XPS), Auger electron spectroscopy, and secondary ion mass spectroscopy can perform chemical analysis but require ultra-high vacuum and expensive equipment (4). Great efforts have been devoted to extending XPS analysis to near ambient conditions (2). Indeed, both near-ambient pressure XPS and extended X-ray absorption fine structure have significantly expanded the applicability of these X-ray–based techniques for understanding reaction mechanisms at chemically active interfaces (2, 5). However, both methods require intense synchrotron radiation to achieve high sensitivity and resolution, which limits their practical accessibility and increases their cost. State-of-the-art surface-sensitive spectroscopy techniques, such as sum frequency generation and second harmonic generation, can perform analysis under ambient conditions but require technically complex equipment such as femtosecond lasers (6). Even with all these techniques available, molecular dynamics or chemical reaction kinetics at surfaces are still challenging to probe experimentally (7) (SI Appendix, Supplementary Note 1).NMR spectroscopy is one of the major tools for chemical and structural analysis in chemistry, biology, and materials science. Solid-state NMR in particular (8) has advanced understanding of a range of systems, including metal organic frameworks (9), batteries (10), and catalysts (11). However, sensitivity remains a challenge for traditional NMR spectroscopy, making studies at surfaces difficult because of the limited numbers of nuclear spins. Recently, surface-enhanced NMR spectroscopy (DNP-SENS) relying on hyperpolarization such as dynamic nuclear polarization (12, 13) or xenon-based techniques (14) gained research momentum and enabled probing spins located at surfaces. However, even in highly porous materials with greater than 1,000 m²/g surface area, the concentration of NMR-active nuclei of interest often remains low (e.g., 1 mmol of surface atoms/g), which requires long averaging times to obtain solid-state NMR spectra with reasonable signal-to-noise ratios (SNR) (12) (SI Appendix, Supplementary Note 2).Here, we demonstrate the use of quantum sensors in diamond as a surface-sensitive spectroscopy technique that works at ambient conditions and can probe planar interfaces on the microscopic length scale with far greater sensitivity (femtomoles, see Materials and Methods) than conventional NMR. The spectroscopic technique relies on the nitrogen vacancy (NV) point defect, consisting of a nitrogen impurity (N) and an adjacent vacancy (V) in the carbon lattice of diamond. These spin-1 defects allow for optical detection of magnetic resonance and have been established as highly sensitive nanoscale magnetic field sensors (15, 16). Near-surface NV centers are sensitive to magnetic fields from the Larmor precession of nuclei from samples positioned outside of the diamond. This enables nanoscale NMR detection—even down to a single molecule (17) or spin (18, 19). The measurement volume of such NV sensors (20, 21) corresponds to a hemisphere whose radius is roughly their depth below the surface in the diamond lattice (e.g., 5 to 10 nm). At this small length scale, the thermal polarization of the nuclear spins can be neglected since spin noise dominates for a small number of spins (22, 23). For that reason, the NMR signal strength is independent of the applied magnetic field B₀, reducing experimental complexity and costs, which makes the technique accessible to a broader community. Previously published nanoscale NV-NMR experiments detected NMR signals from either bulk samples [such as viscous oils (21, 22, 24)] or samples tethered to (17) or placed directly on the diamond surface (25). In this work, we propose the use of NV centers in diamond combined with state-of-the-art thin film deposition techniques as a general platform to detect NMR signals with high sensitivity and spatial resolution even from nondiamond surfaces. This approach is general and allows for the probing of a variety of surfaces and interfaces with NMR, thereby enabling their chemistry to be explored. Here, we use atomic layer deposition (ALD), a technology that can be applied to synthesize films of a wide variety of materials with high thickness precision to coat the diamond with amorphous aluminum oxide (Al₂O₃). Al₂O₃ provides an exemplary surface of high technical relevance in optoelectronic applications and acts as structural support in various catalytic processes (26). In a proof-of-concept study for this surface-sensitive spectroscopic technique, we probe the chemical modification of the Al₂O₃ surface with phosphonate anchoring during the formation of a self-assembling monolayer (SAM) (27).     

Feasibility and Acceptability of ‘VitaVillage’: A Serious Game for Nutrition Education

Computer games have previously been used to improve nutrition knowledge in children. This paper describes the acceptability and feasibility of a serious game, “VitaVillage”, for improving child nutrition knowledge. VitaVillage is a farming-style game in which the player undertakes quests and completes questions aimed at increasing several aspects of nutrition and healthy eating knowledge. Children aged 9–12 years in two primary schools (control vs. intervention) completed a nutrition knowledge questionnaire at baseline (T1) and after 1 week (T2). Participants at the intervention school (n = 75) played VitaVillage for 20 minutes on two occasions. Control participants (n = 94) received no nutrition education. Likeability question scores and written feedback from intervention participants was reported qualitatively. Paired sample t-tests were used to compare T1 and T2 nutrition knowledge changes between control and intervention participants. Engagement with VitaVillage improved children’s overall nutrition knowledge (Mean increase of 2.25 points between T1 and T2, Standard Deviation (SD) 6.31, p = 0.035) compared to controls. The game was liked overall (mean score 77 (SD 24.6) on scale of 0–100) and positive feedback was given. Results indicate that VitaVillage has the potential to be successful as a nutrition education tool. In the future, VitaVillage’s content and gameplay will be revised, extended and evaluated for its long-term impact on eating behaviour and knowledge changes.     

The Interplay of Environmental Exposures and Mental Health: Setting an Agenda

Background: To date, health-effects research on environmental stressors has rarely focused on behavioral and mental health outcomes. That lack of research is beginning to change. Science and policy experts in the environmental and behavioral health sciences are coming together to explore converging evidence on the relationship—harmful or beneficial—between environmental factors and mental health.Objectives: To organize evidence and catalyze new findings, the National Academy of Sciences, Engineering, and Medicine (NASEM) hosted a workshop 2–3 February 2021 on the interplay of environmental exposures and mental health outcomes.Methods: This commentary provides a nonsystematic, expert-guided conceptual review and interdisciplinary perspective on the convergence of environmental and mental health, drawing from hypotheses, findings, and research gaps presented and discussed at the workshop. Featured is an overview of what is known about the intersection of the environment and mental health, focusing on the effects of neurotoxic pollutants, threats related to climate change, and the importance of health promoting environments, such as urban green spaces.Discussion: We describe what can be gained by bridging environmental and psychological research disciplines and present a synthesis of what is needed to advance interdisciplinary investigations. We also consider the implications of the current evidence for a) foundational knowledge of the etiology of mental health and illness, b) toxicant policy and regulation, c) definitions of climate adaptation and community resilience, d) interventions targeting marginalized communities, and e) the future of research training and funding. We include a call to action for environmental and mental health researchers, focusing on the environmental contributions to mental health to unlock primary prevention strategies at the population level and open equitable paths for preventing mental disorders and achieving optimal mental health for all. https://doi.org/10.1289/EHP9889     

A novel bioartificial liver with culture of porcine hepatocyte aggregates under simulated microgravity

An extracorporeal bioartificial liver device could provide vital support to patients suffering from acute liver failure. We designed a novel, customized bioreactor for use as a bioartificial liver (patent pending). The Innsbruck Bioartificial Liver (IBAL) contains aggregates of porcine hepatocytes grown under simulated microgravity. The culture vessel rotates around its longitudinal axis and is perfused by two independent circuits. The circuit responsible for exchange of plasma components with the patient consists of a dialysis tube winding spirally around the internal wall of the culture vessel. IBAL was evaluated in vitro. Viability tests showed sufficient viability of hepatocytes for up to 10 days. Cytologic examination of samples from the bioreactor showed liver cell aggregates. These were also examined by electron microscopy. A number of biochemical parameters were analyzed. In conclusion, cell culture is possible for at least 10 days in the IBAL system, organoid hepatocyte aggregates are formed and synthetic activity of the hepatocytes was demonstrated.     

整合患者导向的测量工具项目编制等距量表实现ICF类目用于评定的可操作化

目的通过整合不同的患者导向的测量工具的项目来编制ICF特定类目的等距量表结构。方法使用有效的122例类风湿关节炎患者的样本资料进行心理测量研究。患者完成6个不同的以患者导向的测量工具。将这些测量工具项目的内容与ICF类目进行匹配。对项目反应等级进行Rasch分析用于检查这些测量工具项目是否说明了ICF类目b130:能量和驱力功能,从而构成一个心理测量可靠的等距量表。结果 19个项目与b130能量和驱力功能有关。根据2χ检验和Z值统计,19个项目中的16个项目拟合Rasch模型(项目和个人的ZMean=0.451,ZSD=1.085和ZMean=-0.223,ZSD=1.132)。Person分离指数rβ是0.93。结论可以构建ICF类目等距量表使得单个ICF类目可操作化。每个项目的原始格式在等距量表中保持不变。本研究在ICF的操作和将来的实施方面迈出了重要的一步。     

Activation of the PGI(2)/IP system contributes to the development of circulatory failure in a rat model of endotoxic shock

Prostacyclin levels are increased in septic patients and several animal models of septic shock, and selective inhibition of cyclooxygenase-2 improved cardiovascular dysfunction in rats treated with lipopolysaccharide (LPS). Here, we examine the specific role of prostacyclin and of the receptor for prostacyclin (IP) in the development of LPS-induced circulatory failure. Intravenous injection of LPS (10 mg/kg) into male Sprague-Dawley rats caused a strong increase in plasma prostacyclin levels, which was paralleled by a decrease in blood pressure and an increase in heart rate. Moreover, LPS injection increased the mRNA expression of the IP receptor in the heart, aorta, lung, liver, adrenal glands, and kidneys. Cotreatment with the IP antagonist CAY-10441 (1, 10, 30, and 100 mg/kg) dose-dependently moderated the LPS-induced changes in mean arterial blood pressure, heart rate, cardiac output, and systemic vascular resistance. The development of cardiovascular failure was ameliorated by CAY-10441 in spite of the typical LPS-induced increases in plasma levels of cytokines and NO. In vitro, cytokines dose- and time-dependently induced IP expression in rat vascular smooth muscle cells. Incubation of cells with the stable IP agonist iloprost in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-mehylxanthine resulted in higher cAMP levels in cytokine-treated cells compared with untreated cells. Taken together, our data demonstrate a prominent role of the prostacyclin/IP system in the development of LPS-induced cardiovascular failure.     

Low frequency of H-ras mutations in hepatocellular adenomas and carcinomas and in hepatoblastomas from B6C3F1 mice exposed to oxazepam in the diet

Oxazepam has been the subject of recent toxicological and carcinogenesisstudies because it is a commonly prescribed tranquilizer andhas been shown to cause tumors in rodents. In this study, maleand female B6C3F1 mice receIved 0,125, 2500 or 5000 p.p.m. oxazepamin the diet for up to 2 years. Hepatocellular adenomas and carcinomas,as well as hepatoblastomas, which developed in these mice, wereexamined for the presence of activated ms proto-oncogenes. DNAwas Isolated from 20 or more tumors from each exposure groupand analyzed by oligonudeotide hybridiza tion, single-strandedconformation polymorphism analysis and direct sequencing ofPCR-ampllfied H-ms gene fragments for codon 61 mutations. Thirteenof 37 (35%) hepatocellular adenomas and carcinomas from the125 p.p.m. exposure group had mutations in codon 61, while mutationswere detected in only 2 of 25 or 8% of the liver tumors fromthe 2500 p.p.m. exposure group and none of the 22 tumors fromthe 5000 p.p.m. group. This compares to 63% of 126 historIcalcontrol liver tumors and 55% of 20 liver tumors from unexposedB6C3F1 mice in this study. In addition, 12 hepatoblastomas fromthe two high dose groups were examined for H-ras mutations atcodon 61, but none were detected. No tumor DNAs from any ofthe exposure groups tested had mutations In codons 12, 13 or117 of the H-ras gene or codons 12 or 13 of the K-ras gene,the other known hotspots for ras activation in mouse liver tumors.These results, together with those from the National ToxicologyProgram study showing no evidence of cytotoxicity or genotoxicityby oxazepam, suggest that oxazepam preferentially promotes cellsthat have activating lesions other than ras.