Measurement of gut permeability using fluorescent tracer agent technology

Abstract The healthy gut restricts macromolecular and bacterial movement across tight junctions, while increased intestinal permeability accompanies many intestinal disorders. Dual sugar absorption tests, which measure intestinal permeability in humans, present challenges. Therefore, we asked if enterally administered fluorescent tracers could ascertain mucosal integrity, because transcutaneous measurement of differentially absorbed molecules could enable specimen-free evaluation of permeability. We induced small bowel injury in rats using high- (15 mg/kg), intermediate- (10 mg/kg), and low- (5 mg/kg) dose indomethacin. Then, we compared urinary ratios of enterally administered fluorescent tracers MB-402 and MB-301 to urinary ratios of sugar tracers lactulose and rhamnose. We also tested the ability of transcutaneous sensors to measure the ratios of absorbed fluorophores. Urinary fluorophore and sugar ratios reflect gut injury in an indomethacin dose dependent manner. The fluorophores generated smooth curvilinear ratio trajectories with wide dynamic ranges. The more chaotic sugar ratios had narrower dynamic ranges. Fluorophore ratios measured through the skin distinguished indomethacin-challenged from same day control rats. Enterally administered fluorophores can identify intestinal injury in a rat model. Fluorophore ratios are measureable through the skin, obviating drawbacks of dual sugar absorption tests. Pending validation, this technology should be considered for human use

Escherichia coli O157 Exposure in Wyoming and Seattle: Serologic Evidence of Rural Risk

We tested the hypothesis that rural populations have increased exposure to Escherichia coli O157:H7. We measured circulating antibodies against the O157 lipopolysaccharide in rural Wyoming residents and in blood donors from Casper, Wyoming, and Seattle, Washington, by enzyme immunoassay (EIA). EIA readings were compared by analysis of variance and the least squares difference multiple comparison procedure. Rural Wyoming residents had higher antibody levels to O157 LPS than did Casper donors, who, in turn, had higher levels than did Seattle donors (respective least squares means: 0.356, 0.328, and 0.310; p<0.05, Seattle vs. Casper, p<0.001, rural Wyoming vs. either city). Lower age was significantly correlated with EIA scores; gender; and, in rural Wyoming, history of bloody diarrhea, town, duration of residence, and use of nontreated water at home were not significantly correlated. These data suggest that rural populations are more exposed to E. coli O157:H7 than urban populations

Transdermal fluorescence detection of a dual fluorophore system for noninvasive point-of-care gastrointestinal permeability measurement

The intestinal mucosal barrier prevents macromolecules and pathogens from entering the circulatory stream. Tight junctions in this barrier are compromised in inflammatory bowel diseases, environmental enteropathy, and enteric dysfunction. Dual sugar absorption tests are a standard method for measuring gastrointestinal integrity, however, these are not clinically amenable. Herein, we report on a dual fluorophore system and fluorescence detection instrumentation for which gastrointestinal permeability is determined in a rat small bowel disease model from the longitudinal measured transdermal fluorescence of each fluorophore. This fluorophore technology enables a specimen-free, noninvasive, point-of-care gastrointestinal permeability measurement which should be translatable to human clinical studies

Does menopause transition influence viral suppression and adherence in Women living with HIV?

BACKGROUND Increasing numbers of women living with HIV transition through menopause. It is unclear if this transition has an impact on treatment adherence, viral suppression, psychiatric comorbidities or drug use. We aimed at examining adherence and viral suppression during the perimenopausal period and explored the influence of psychiatric comorbidities and active injection drug use (IDU). SETTING Retrospective Swiss HIV Cohort Study analysis from 01/2010 to 12/2018. METHODS We explored peri- and postmenopausal trends of viral blips, low-level viremia, viral failure, adherence, psychiatric comorbidities and IDU using interrupted time series (ITS) models. RESULTS Rates of depression and psychiatric care increased during perimenopause before decreasing afterwards. Negative treatment outcomes such as viral blips, low-level viremia, viral failure and low adherence steadily declined while transitioning through menopause - this was also true for subgroups of women with depression, psychiatric treatment and active IDU. CONCLUSIONS Increased rates of depression and psychiatric care while transitioning through menopause do not result in lower rates of adherence or viral suppression in women living with HIV in Switzerland

Longer fixation duration while viewing face images

The spatio-temporal properties of saccadic eye movements can be influenced by the cognitive demand and the characteristics of the observed scene. Probably due to its crucial role in social communication, it is argued that face perception may involve different cognitive processes compared with non-face object or scene perception. In this study, we investigated whether and how face and natural scene images can influence the patterns of visuomotor activity. We recorded monkeys’ saccadic eye movements as they freely viewed monkey face and natural scene images. The face and natural scene images attracted similar number of fixations, but viewing of faces was accompanied by longer fixations compared with natural scenes. These longer fixations were dependent on the context of facial features. The duration of fixations directed at facial contours decreased when the face images were scrambled, and increased at the later stage of normal face viewing. The results suggest that face and natural scene images can generate different patterns of visuomotor activity. The extra fixation duration on faces may be correlated with the detailed analysis of facial features

Priming of plane-rotated objects depends on attention and view familiarity

Three experiments investigated the role of attention in visual priming across rotations in the picture plane. Experiment 1 showed that naming latencies increased with the degree of misorientation for objects commonly seen in an upright view (base objects) but not for objects seen familiarly from many views (no-base objects). In Experiment 2, no-base objects revealed a priming pattern identical to that observed previously for left-right reflections (Stankiewicz, Hummel, & Cooper, 1998): Attended objects primed themselves in the same and rotated views, whereas ignored images primed themselves only in the same view, with additive effects of attention and orientation. In Experiment 3 ignored base objects only primed themselves in a familiar (upright) view, indicating that priming only obtains when that image makes contact with object memory. These data challenge theories of object recognition that rely on any single representation of shape and contribute to evidence suggesting holistic (view-like) representations for ignored and analytic (view-insensitive) representations for attended objects

Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs

A systematic review on the effects of group singing on persistent pain in people with long‐term health conditions

Singing can have a range of health benefits; this paper reviews the evidence of the effects of group singing for chronic pain in people with long‐term health conditions. We searched for published peer‐reviewed singing studies reporting pain measures (intensity, interference and depression) using major electronic databases (last search date 31 July 2018). After screening 123 full texts, 13 studies met the inclusion criteria: five randomized controlled trials (RCTs), seven non‐RCTs and one qualitative study. Included studies were appraised using Downs and Black and the Critical Appraisals Skills Programme quality assessments. Included studies reported differences in the type of singing intervention, long‐term condition and pain measures. Due to the high heterogeneity, we conducted a narrative review. Singing interventions were found to reduce pain intensity in most studies, but there was more equivocal support for reducing pain interference and depression. Additionally, qualitative data synthesis identified three key linked and complementary themes: physical, psychological and social benefits. Group singing appears to have the potential to reduce pain intensity, pain interference and depression; however, we conclude that there is only partial support for singing on some pain outcomes based on the limited available evidence of varied quality. Given the positive findings of qualitative studies, this review recommends that practitioners are encouraged to continue this work. More studies of better quality are needed. Future studies should adopt more robust methodology and report their singing intervention in details. Group singing may be an effective and safe approach for reducing persistent pain and depression in people with long‐term health conditions.Health and Social Care Research Centr