Circulating Th17, Th22, and Th1 Cells Are Increased in Psoriasis

Th17, Th22, and Th1 cells are detected in psoriatic skin lesions and implicated in psoriasis pathogenesis, but inflammatory T cell numbers in blood, as well as the relative importance of each cell type, is unclear. Using 7-color flow cytometry, circulating Th17, Th22, and Th1 cells were quantified in 21 untreated psoriatics and 17 healthy individuals. CCR6 was the best cell surface marker for IL-17A+ cells when compared with IL-23R or CD161. CCR6+, IL-17A+, IL-22+, CCR6+IL-17A+, CCR6+IL-22+, CCR6+tumor necrosis factor-α+, IL-17A+IFN-γ-, IL-17A+IL-22+IFN-γ-, and IL-17A+IL-22-IFN-γ- cells were increased in psoriatics (all values P<0.001), indicating elevations in circulating Th17 cells, using multiple criteria to define these cells. Th22 (IL-17A-IL-22+IFN-γ-, P<0.05) and Th1 (IL-17A-IFN-γ+, P<0.05) cells were also increased in psoriatics, but to a lesser extent. Inhibition of either NF-κB or STAT3 in vitro blocked cytokine production by both Th17 and Th1 cells. Circulating levels of Th17 and Th1 cells decreased in a subset of five psoriasis patients serially evaluated following induction therapy with infliximab. In summary, elevated numbers of circulating inflammatory T cells may contribute to cutaneous inflammation and systemic inflammatory disease that occurs in individuals with psoriasis

Supporting Solidarity: Appraising and Collecting Online Content Surrounding the Women's Marches in Maryland

Report and presentation from the MARAC conference in Buffalo, NY on October 28, 2017. S23, "Documenting Social Protest: Lessons Learned from the Women's March." This project took place in the context of an entire course on archival appraisal at the University of Maryland and had powerful implications for archival outreach as activism as well as the tools needed to carry out collection development for born-digital materials. We used Archive-It to crawl social media pages and decided to focus on local solidarity marches in Maryland as the national Women's March was already well-documented. As students, we learned that activism and outreach are integral to the archival profession; we have to be able to explain why we as archivists want to document social protest

Glucose Control, Sleep, Obesity, and Real-World Driver Safety at Stop Intersections in Type 1 Diabetes

Background: Diabetes is associated with obesity, poor glucose control and sleep dysfunction which impair cognitive and psychomotor functions, and, in turn, increase driver risk. How this risk plays out in the real-world driving settings is terra incognita. Addressing this knowledge gap requires comprehensive observations of diabetes driver behavior and physiology in challenging settings where crashes are more likely to occur, such as stop-controlled traffic intersections, as in the current study of drivers with Type 1 Diabetes (T1DM). Methods: 32 active drivers from around Omaha, NE participated in 4-week, real-world study. Each participant's own vehicle was instrumented with an advanced telematics and camera system collecting driving sensor data and video. Videos were analyzed using computer vision models detecting traffic elements to identify stop signs. Stop sign detections and driver stopping trajectories were clustered to geolocate and extract driver-visited stop intersections. Driver videos were then annotated to record stopping behavior and key traffic characteristics. Stops were categorized as safe or unsafe based on traffic law. Results: Mixed effects logistic regression models examined how stopping behavior (safe vs. unsafe) in T1DM drivers was affected by 1) abnormal sleep, 2) obesity, and 3) poor glucose control. Model results indicate that one standard deviation increase in BMI (~7 points) in T1DM drivers associated with a 14.96 increase in unsafe stopping odds compared to similar controls. Abnormal sleep and glucose control were not associated with increased unsafe stopping. Conclusion: This study links chronic patterns of abnormal T1DM driver physiology, sleep, and health to driver safety risk at intersections, advancing models to identify real-world safety risk in diabetes drivers for clinical intervention and development of in-vehicle safety assistance technology.Comment: 23 pages, 7 figures, 10 table

Quantifying vehicle control from physiology in type 1 diabetes

Objective: Our goal is to measure real-world effects of at-risk driver physiology on safety-critical tasks like driving by monitoring driver behavior and physiology in real-time. Drivers with type 1 diabetes (T1D) have an elevated crash risk that is linked to abnormal blood glucose, particularly hypoglycemia. We tested the hypotheses that (1) T1D drivers would have overall impaired vehicle control behavior relative to control drivers without diabetes, (2) At-risk patterns of vehicle control in T1D drivers would be linked to at-risk, in-vehicle physiology, and (3) T1D drivers would show impaired vehicle control with more recent hypoglycemia prior to driving. Methods: Drivers (18 T1D, 14 control) were monitored continuously (4 weeks) using in-vehicle sensors (e.g., video, accelerometer, speed) and wearable continuous glucose monitors (CGMs) that measured each T1D driver’s real-time blood glucose. Driver vehicle control was measured by vehicle acceleration variability (AV) across lateral (AVY, steering) and longitudinal (AVX, braking/accelerating) axes in 45-second segments (N = 61,635). Average vehicle speed for each segment was modeled as a covariate of AV and mixed-effects linear regression models were used. Results: We analyzed 3,687 drives (21,231 miles). T1D drivers had significantly higher overall AVX, Y compared to control drivers (BX = 2.5 × 10−2 BY = 1.6 × 10−2, p \u3c 0.01)—which is linked to erratic steering or swerving and harsh braking/accelerating. At-risk vehicle control patterns were particularly associated with at-risk physiology, namely hypo- and hyperglycemia (higher overall AVX,Y). Impairments from hypoglycemia persisted for hours after hypoglycemia resolved, with drivers who had hypoglycemia within 2–3 h of driving showing higher AVX and AVY. State Department of Motor Vehicle records for the 3 years preceding the study showed that at-risk T1D drivers accounted for all crashes (N = 3) and 85% of citations (N = 13) observed. Conclusions: Our results show that T1D driver risk can be linked to real-time patterns of at-risk driver physiology, particularly hypoglycemia, and driver risk can be detected during and prior to driving. Such naturalistic studies monitoring driver vehicle controls can inform methods for early detection of hypoglycemia-related driving risks, fitness to drive assessments, thereby helping to preserve safety in at-risk drivers with diabetes

Coconut and sunflower oil ratios in ice cream influence subsequent food selection and intake

The effect of coconut oil (CO, containing mainly medium chain triglycerides - MCTs) and sunflower oil (SO, containing mainly long chain triglycerides - LCTs) used as fat source (10% fat ice cream) in different ratios (25% CO and 75% SO - 25CO:75SO, 50% CO and 50% SO - 50CO:50SO, 75% CO and 25% SO - 75CO:25SO) was investigated to assess differences in appetite and ad-libitum (evening and snack) food intake using a single blind design. 36 healthy female participants consumed a fixed portion (150 g) of ice cream 45 min before an ad-libitum dinner and snacks. Appetite sensations were tracked across the day. Participants ate significantly less fat after 75CO:25SO than 25CO:75SO (p = 0.007) and there was also a trend for lower fat intake in this condition as compared to 50CO:50SO (p = 0.068). High fat savoury snack intake significantly decreased after 75CO:25SO in comparison with both 25CO:75SO (p = 0.038) and 50CO:50SO (p = 0.008). Calorie intake from snacks was also found to be significantly lower after 25CO:75SO and 50CO:50SO than 75CO:25SO (p = 0.021 and 0.030 respectively). There was no effect of condition on appetite or desire ratings over the day. Eating a standard portion of ice cream containing different ratios of MCTs and LCTs can modestly influence acute food selection and intake, with MCTs manifesting their effect earlier and LCTs later due to differences in the absorption and metabolism of these lipids. However, the differences evident in the present study were small, and require further research before firm conclusions can be drawn

An updated re-entry analysis of the Hubble Space Telescope

The Hubble Space Telescope (HST), launched in 1990, has without question given us a better understanding of the Universe [1]. The storied spacecraft has far exceeded its design life and, in spite of four repair missions, is nearing the end of its useful lifespan. Originally designed to be returned by the Space Shuttle, the HST has no on-board propulsion system. A 2012 study estimated that without intervention, the HST will re-enter the atmosphere in approximately 2027 with a 1:240 risk of fatality [2]. This study updates that analysis with more recent de-orbit technologies and updated trajectory information. We propose a design solution to safely perform a targeted de-orbit, assuming a worst-case scenario (a non-functional, tumbling spacecraft). Multiple de-orbit options are assessed to actively capture the satellite. Results frame an approach that could be accomplished with proven technologies at reasonable cost to improve the fatality risk as required by US Government regulation [3]. Moreover, delayed action would significantly increase mission cost and complexity so we recommend a project start in the near future

Circulating endocannabinoids during hematopoietic stem cell transplantation: A pilot study

AbstractObjectiveHematopoietic stem cell transplantation (HCT) is a stressful and rigorous medical procedure involving significant emotional and immune challenges. The endocannabinoid (eCB) signaling system is involved in regulation of both the immune system and emotional reactivity, yet little is known about its function during HCT. We investigated the role of the eCB signaling system in a group of HCT recipients.MethodsA total of 19 HCT recipients were enrolled and provided psychosocial data and blood samples at three peri-transplant time points: prior to transplant, hospital discharge, and approximately 100 days post-transplant. Psychosocial factors, inflammatory molecules, and the eCBs were determined and assessed for changes over this period and association with each other.ResultsHCT recipients demonstrated significant changes over the peri-transplant period in inflammatory molecules and psychosocial functioning, but not in circulating concentrations of the eCBs. Associations among these variables were most likely to be present pre-transplant and least likely to be present immediately post-transplant, with depressive symptoms and inflammation most significantly associated. The eCB 2-arachidonoylglycerol (2-AG) was significantly, positively associated with both interleukin (IL)-6 and C-reactive protein (CRP) and negatively associated with depressive symptoms.ConclusionsThe eCB signaling system may have alternative sources and regulatory mechanisms in addition to the immune system. Given the significant associations with inflammatory molecules and depressive symptoms in the peri-transplant period, it is important to better understand this system and its potential implications in the setting of complex and stressful medical procedures such as HCT

Integrated analysis of the molecular pathogenesis of FDXR-associated disease.

The mitochondrial flavoprotein ferredoxin reductase (FDXR) is required for biogenesis of iron-sulfur clusters and for steroidogenesis. Iron-sulfur (Fe-S) clusters are ubiquitous cofactors essential to various cellular processes, and an increasing number of disorders are associated with disruptions in the synthesis of Fe-S clusters. Our previous studies have demonstrated that hypomorphic mutations in FDXR cause a novel mitochondriopathy and optic atrophy in humans and mice, attributed in part to reduced function of the electron transport chain (ETC) as well as elevated production of reactive oxygen species (ROS). Inflammation and peripheral neuropathy are also hallmarks of this disease. In this paper, we demonstrate that FDXR mutation leads to significant optic transport defects that are likely to underlie optic atrophy, a major clinical presentation in FDXR patients, as well as a neurodegenerative loss of cells in the central nervous system (CNS). Molecular analysis indicates that FDXR mutation also leads to mitochondrial iron overload and an associated depolarization of the mitochondrial membrane, further supporting the hypothesis that FDXR mutations cause neurodegeneration by affecting FDXR\u27s critical role in iron homeostasis