Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light—stimuli at extreme ends of the circadian system’s dose–response ...curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30–300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose–response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18–30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10–2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock’s role in human health and disease.
•It provides recommendations for risk reduction and screening in hereditary breast and ovarian cancer syndrome.•It focuses on risk reduction and screening mainly in unaffected carriers and ...high-resource settings.•The panel encompasses an international multidisciplinary group of experts.•Recommendations are based on available scientific data and the authors’ collective expert opinion.
Microbes have remarkable capabilities to attach to the surface of implanted medical devices and form biofilms that adversely impact device function and increase the risk of multidrug-resistant ...infections. The physicochemical properties of biomaterials have long been known to play an important role in biofilm formation. More recently, a series of discoveries in the natural world have stimulated great interest in the use of 3D surface topography to engineer antifouling materials that resist bacterial colonization. There is also increasing evidence that some medical device surface topographies, such as those designed for tissue integration, may unintentionally promote microbial attachment. Despite a number of reviews on surface topography and biofilm control, there is a missing link between how bacteria sense and respond to 3D surface topographies and the rational design of antifouling materials. Motivated by this gap, we present a review of how bacteria interact with surface topographies, and what can be learned from current laboratory studies of microbial adhesion and biofilm formation on specific topographic features and medical devices. We also address specific biocompatibility considerations and discuss how to improve the assessment of the anti-biofilm performance of topographic surfaces. We conclude that 3D surface topography, whether intended or unintended, is an important consideration in the rational design of safe medical devices. Future research on next-generation smart antifouling materials could benefit from a greater focus on translation to real-world applications.
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Abstract
Study Objectives
Sleep regularity predicts many health-related outcomes. Currently, however, there is no systematic approach to measuring sleep regularity. Traditionally, metrics have ...assessed deviations in sleep patterns from an individual’s average; these traditional metrics include intra-individual standard deviation (StDev), interdaily stability (IS), and social jet lag (SJL). Two metrics were recently proposed that instead measure variability between consecutive days: composite phase deviation (CPD) and sleep regularity index (SRI). Using large-scale simulations, we investigated the theoretical properties of these five metrics.
Methods
Multiple sleep–wake patterns were systematically simulated, including variability in daily sleep timing and/or duration. Average estimates and 95% confidence intervals were calculated for six scenarios that affect the measurement of sleep regularity: “scrambling” the order of days; daily vs. weekly variation; naps; awakenings; “all-nighters”; and length of study.
Results
SJL measured weekly but not daily changes. Scrambling did not affect StDev or IS, but did affect CPD and SRI; these metrics, therefore, measure sleep regularity on multi-day and day-to-day timescales, respectively. StDev and CPD did not capture sleep fragmentation. IS and SRI behaved similarly in response to naps and awakenings but differed markedly for all-nighters. StDev and IS required over a week of sleep–wake data for unbiased estimates, whereas CPD and SRI required larger sample sizes to detect group differences.
Conclusions
Deciding which sleep regularity metric is most appropriate for a given study depends on a combination of the type of data gathered, the study length and sample size, and which aspects of sleep regularity are most pertinent to the research question.
Microbial colonization of medical devices is a widespread problem that tests the limits of conventional analytical methods. Successful analytical endeavors require collaboration between clinicians, ...microbiologists, biomedical engineers, and analytical chemists.
Objective. A challenge for implementing high bandwidth cortical brain-machine interface devices in patients is the limited functional lifespan of implanted recording electrodes. Development of ...implant technology currently requires extensive non-clinical testing to demonstrate device performance. However, testing the durability of the implants in vivo is time-consuming and expensive. Validated in vitro methodologies may reduce the need for extensive testing in animal models. Approach. Here we describe an in vitro platform for rapid evaluation of implant stability. We designed a reactive accelerated aging (RAA) protocol that employs elevated temperature and reactive oxygen species (ROS) to create a harsh aging environment. Commercially available microelectrode arrays (MEAs) were placed in a solution of hydrogen peroxide at 87 °C for a period of 7 days. We monitored changes to the implants with scanning electron microscopy and broad spectrum electrochemical impedance spectroscopy (1 Hz-1 MHz) and correlated the physical changes with impedance data to identify markers associated with implant failure. Main results. RAA produced a diverse range of effects on the structural integrity and electrochemical properties of electrodes. Temperature and ROS appeared to have different effects on structural elements, with increased temperature causing insulation loss from the electrode microwires, and ROS concentration correlating with tungsten metal dissolution. All array types experienced impedance declines, consistent with published literature showing chronic (>30 days) declines in array impedance in vivo. Impedance change was greatest at frequencies <10 Hz, and smallest at frequencies 1 kHz and above. Though electrode performance is traditionally characterized by impedance at 1 kHz, our results indicate that an impedance change at 1 kHz is not a reliable predictive marker of implant degradation or failure. Significance. ROS, which are known to be present in vivo, can create structural damage and change electrical properties of MEAs. Broad-spectrum electrical impedance spectroscopy demonstrates increased sensitivity to electrode damage compared with single-frequency measurements. RAA can be a useful tool to simulate worst-case in vivo damage resulting from chronic electrode implantation, simplifying the device development lifecycle.
Abstract
We report on calcium abundance
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(Ca) estimates during the decay phases of 194 solar X-ray flares using archived data from the Bent Crystal Spectrometer (BCS) on the Solar Maximum Mission ...(operational 1980–1989). The abundances are derived from the ratio of the total calcium X-ray line emission in BCS channel 1 to that in neighboring continuum, with temperature from a satellite-to-resonance line ratio. Generally, the calcium abundance is found to be about 3 times the photospheric abundance, as previously found, indicating a “first ionization potential” (FIP) effect for calcium, which has a relatively low FIP value. The precision of the abundance estimates (referred to hydrogen on a logarithmic scale with
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(H) = 12), is typically ∼± 0.01, enabling any time variations of
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(Ca) during the flare decay to be examined. For a total of 270 short time segments with
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(Ca) determined to better than 2.3% accuracy, many (106; 39%) showed variations in
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(Ca) at the 3
σ
level. For the majority, in 74 (70%) of these 106 segments
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(Ca) decreased with time, and for 32 (30%)
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(Ca) increased with time. For 79 out of 270 (29%) we observed constant or nearly constant
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(Ca), and the remaining 85 (31%) with irregular time behavior. A common feature was the presence of discontinuities in the time behavior of
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(Ca). Relating these results to the ponderomotive force theory of Laming, we attribute the nature of varying
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(Ca) to the emergence of loop structures in addition to the initial main loop, each with its characteristic calcium abundance.
The association of irregular sleep schedules with circadian timing and academic performance has not been systematically examined. We studied 61 undergraduates for 30 days using sleep diaries, and ...quantified sleep regularity using a novel metric, the sleep regularity index (SRI). In the most and least regular quintiles, circadian phase and light exposure were assessed using salivary dim-light melatonin onset (DLMO) and wrist-worn photometry, respectively. DLMO occurred later (00:08 ± 1:54 vs. 21:32 ± 1:48; p < 0.003); the daily sleep propensity rhythm peaked later (06:33 ± 0:19 vs. 04:45 ± 0:11; p < 0.005); and light rhythms had lower amplitude (102 ± 19 lux vs. 179 ± 29 lux; p < 0.005) in Irregular compared to Regular sleepers. A mathematical model of the circadian pacemaker and its response to light was used to demonstrate that Irregular vs. Regular group differences in circadian timing were likely primarily due to their different patterns of light exposure. A positive correlation (r = 0.37; p < 0.004) between academic performance and SRI was observed. These findings show that irregular sleep and light exposure patterns in college students are associated with delayed circadian rhythms and lower academic performance. Moreover, the modeling results reveal that light-based interventions may be therapeutically effective in improving sleep regularity in this population.
The rate of gastric emptying is a critical determinant of postprandial glycaemia and, accordingly, is fundamental to maintaining blood glucose homeostasis. Disordered gastric emptying occurs ...frequently in patients with longstanding type 1 diabetes mellitus and type 2 diabetes mellitus (T2DM). A complex bidirectional relationship exists between gastric emptying and glycaemia--gastric emptying accounts for ∼35% of the variance in peak postprandial blood glucose concentrations in healthy individuals and in patients with diabetes mellitus, and the rate of emptying is itself modulated by acute changes in glycaemia. Clinical implementation of incretin-based therapies for the management of T2DM, which diminish postprandial glycaemia, in part by slowing gastric emptying, is widespread. Other therapies for patients with T2DM, which specifically target gastric emptying include pramlintide and dietary-based treatment approaches. A weak association exists between upper gastrointestinal symptoms and the rate of gastric emptying. In patients with severe diabetic gastroparesis, pathological changes are highly variable and are characterized by loss of interstitial cells of Cajal and an immune infiltrate. Management options for patients with symptomatic gastroparesis remain limited in their efficacy, which probably reflects the heterogeneous nature of the underlying pathophysiology.
Summary Objective These studies investigated cytokine and chemokine receptor profiles in nucleus pulposus (NP) cells, and the effects of receptor stimulation on mRNA levels of extracellular matrix ...(ECM) components, degrading enzymes and cytokine and chemokine expression. Method Immunohistochemistry (IHC) was performed to localise expression of CD4, CCR1, CXCR1 and CXCR2 in human NP tissue samples. Effects of cytokine and chemokine stimulation was performed to investigate effects related to ECM remodelling and modulation of cytokine and chemokine mRNA expression. Results IHC identified CD4, CCR1, CXCR1 and CXCR2 expression by NP cells. Differential expression profiles were observed for CD4 and CXCR2 in tissue samples from degenerate and infiltrated IVDs. In vitro stimulations of primary human NP cultures with IL-16, CCL2, CCL3, CCL7 or CXCL8 did not identify any modulatory effects on parameters associated with ECM remodelling or expression of other cytokines and chemokines. Conversely, IL-1 was seen to modulate ECM remodelling and expression of all other cytokines and chemokines investigated. Conclusion This study demonstrates for the first time that NP cells express a number of cytokine and chemokine receptors and thus could respond in an autocrine or paracrine manner to cytokines and chemokines produced by NP cells, particularly during tissue degeneration. However, this study failed to demonstrate regulatory effects on ECM genes and degradative enzymes or other cytokines and chemokines for any target investigated, with the exception of IL-1. This suggests that IL-1 is a master regulator within the IVD and may exert regulatory potential over a plethora of other cytokines and chemokines.
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