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Glenn S Corbin,1 David L Kading,2 Sean M Powell,3 Brian D Rosenblatt,4 Glenda B Secor,5 Cecile A Maissa,6 Renee J Garofalo71Wyomissing Optometric Center, Wyomissing, PA, USA; 2Specialty Eyecare Group, Kirkland, WA, USA; 320/20 Eye Care LLC, Lenexa, KS, USA; 4Rosenblatt Family Eye Care Associates, Raritan, NJ, USA; 5Huntington Beach, CA, USA; 6OTG Research and Consultancy, London, UK; 7Alcon Research Ltd, Fort Worth, TX, USABackground: The purpose of this study was to evaluate the safety and efficacy of a new multi-purpose disinfecting solution containing a diblock copolymer, poly(oxyethylene)-poly(oxybutylene), designed to improve the wetting properties of silicone hydrogel lenses in patients with symptoms of discomfort.Methods: This 30-day, randomized, concurrently controlled, double-masked, multi-site study involved 589 subjects at 42 investigational sites in the US. Existing symptomatic lens wearers were randomly assigned to either regimen 1 (OPTI-FREE® PureMoist®, Alcon Laboratories Inc,) a newly developed formulation containing the diblock copolymer), or regimen 2 (renu® fresh™ multi-purpose solution Bausch + Lomb, Inc). On days 0, 14 and 30, subjects assessed acceptability and comfort using seven Likert-type questions, rated the intensity of ocular symptoms (comfort, dryness, irritation, scratchiness, burning, stinging) on a visual analog scale (0–100), as well as reported lens wearing time, comfortable lens wearing time, and rewetting drop frequency. The investigators assessed slit-lamp findings (including circumlimbal conjunctival lissamine green staining and corneal fluorescein staining), on-eye lens surface wettability and deposits, visual acuity, and adverse events.Results: Differences favoring regimen 1 were noted on Day 30 for the primary Likert statement “I can comfortably wear my lenses” (P = 0.047) and for comfortable lens wear time (P = 0.041). Symptoms of ocular scratchiness, ocular burning, and ocular stinging were all rated lower after 30 days of use by subjects using regimen 1 compared with those using regimen 2 (P ≤ 0.024). Circumlimbal conjunctival staining (sum score) was significantly lower with regimen 1 (P < 0.0001). Other parameters did not show any difference between the two treatment regimens.Conclusion: This study shows that the new multi-purpose disinfecting solution is safe and effective when used by symptomatic silicone hydrogel contact lens wearers. By improving symptoms of scratchiness, burning, stinging, and comfortable wear time, and decreasing circumlimbal conjunctival staining, the new multi-purpose disinfecting solution enhances the patient's wearing experience and helps maintain optimal lens performance.Keywords: multi-purpose disinfecting solution; subjective comfort; silicone hydrogel contact lenses

This study aimed to determine the relationship between bone mineral content, habitual physical activity, and calcium intake in children. Fifty-seven children, aged 8-11 years, wore pedometers for seven days to assess activity. Calcium intake was estimated by a 4-day food diary. Bone mineral content (BMC) and areal density (BMD) were measured at the total proximal femur and femoral neck using dual energy X-ray absorptiometry. Regression analysis was used to assess contributions of physical activity and calcium intake to BMC, residualized for bone area and body mass. Physical activity explained 11.6% of the variance in residualized BMC at the proximal femur and 14.3% at the femoral neck (p < 0.05). Calcium intake added to the variance explained at the proximal femur only (9.8%, p < 0.05). This study provides evidence for an association between BMC and habitual physical activity. [ABSTRACT FROM AUTHOR]

CREW RESOURCE MANAGEMENT (CRM) has been used for more than 20 years in the aviation industry to teach individual error countermeasures by developing nontechnical tie, cognitive, social) skills based on the observed traits of successful individuals and crews.THE HEALTH CARE INDUSTRY began to investigate aviation CRM after the Institute of Medicine's report, To Err is Human: Building a Safer Health System, recommended that medicine adopt aviation's approach to safety and error management.INITIAL RESULTS of implementing CRM in health care arenas have demonstrated reduced adverse outcomes, reduced errors, reduced length of stay, improved nurse retention, and changed attitudes and behaviors toward teamwork. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate the reliability and variability of eight RT3 accelerometers. METHODS: The RT3 were subjected to two repeated trials of six activities: rest, walking (4 and 6 km x h-1), running (8 and 10 km x h-1), and sit-stand position (20 min). One person performed all trials (female: age 24 yr, height 158.0 cm, mass 48.2 kg). Each activity lasted 12 min. The middle 10 min were taken from each 12-min trial and used as the output measure (cts x min-1). Data were analyzed for activity ( 6), monitor ( 8), and trial ( 2) effects using four three-way ANOVA: vector magnitude, X (vertical), Y (anterioposterior), and Z (mediolateral) axes. RESULTS: Intermonitor coefficient of variation was <6% during locomotive activities, however, increased to 8-25% during sit-stand. A three-way interaction was found for vector magnitude (F35,315=88945.7, P < 0.001) and Y (F35,315=978435.6, P < 0.001) and Z axes (F35,315=103802.8, P < 0.001). A two-way activity x monitor interaction was found for the X axis (F35,315=1037787.0, P < 0.001). Follow-up tests revealed no differences between trials 1 and 2 for vector magnitude, X and Z axes. One monitor recorded significantly lower activity counts in trial 1 compared with trial 2 along the Y axis. Intermonitor differences were evident at 4, 6, 8, and 10 km x h-1 for the Y and Z axes, and at 6, 8, and 10 km x h-1 for the vector magnitude and X axis. Variability between monitors at each activity increased as intensity increased. CONCLUSION: Reliability of the RT3 is good; however, intermonitor variability exists. The vertical axis of the RT3 accelerometer showed the least variability and was the most reliable. It is recommended that intermonitor variability and reliability of RT3 on each axis be assessed before use. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate the technical performance of the RT3 triaxial accelerometer. METHODS: Twenty-three RT3 accelerometers were subjected to a specific vibration along each sensitive axis in isolation, using a motorized vibration table that produced frequencies of 2.1, 5.1, and 10.2 Hz, respectively. Data were analyzed for frequency and axis effects and inter- and intra-instrument variability. RESULTS: ANOVA showed a frequency by axis interaction (F2.1,36.8 = 19.9, P < 0.001). Post hoc tests revealed the Y axis count to be significantly higher than the X and Z axes counts at 5.1 and 10.2 Hz. There was no difference in counts between axes at 2.1 Hz. Interinstrument coefficients of variation (CV) decreased as frequency increased (21.9 to 26.7% at 2.1 Hz, 6.3 to 9.0% at 5.1 Hz, and 4.2 to 7.2% at 10.2 Hz). The intraclass correlation (ICC) between RT3s was 0.99, regardless of the axis. Intra-instrument CV also decreased as frequency increased (2.1 to 56.2%, 0.3 to 2.5%, and 0.2 to 2.9% at 2.1, 5.1, and 10.2 Hz, respectively. CONCLUSION: There were no differences in counts recorded on the X, Y, and Z axes at 2.1 Hz; however, the counts recorded along the Y axis were significantly higher than the counts at the X and Z axes at 5.1 and 10.2 Hz. Due to large coefficients of variation for both inter- and intra-instrument variability at 2.1 Hz, testing the inter- and intra-instrument variability of the accelerometers before use is recommended. [ABSTRACT FROM AUTHOR]

Lentil (Lens culinaris Medik.) is a nutritious food and a staple for millions of people. Not only are lentils a good source of energy, they also contain a range of micronutrients and prebiotic carbohydrates. Kale (Brassica oleracea v. acephala) has been considered as a health food, but its full range of benefits and composition has not been extensively studied. Recent studies suggest that foods are enrich in prebiotic carbohydrates and dietary fiber that can potentially reduce risks of non-communicable diseases, including obesity, cancer, heart disease, and diabetes. Lentil and kale added to a cereal-based diet would enhance intakes of essential minerals and vitamins to combat micronutrient malnutrition. This review provides an overview of lentil and kale as a complementary nutrient-rich whole food source to combat global malnutrition and calorie issues. In addition, prebiotic carbohydrate profiles and the genetic potential of these crops for further micronutrient enrichment are briefly discussed with respect to developing sustainable and nutritious food systems.

Purpose : Because obesity has not responded well to instructing affected adults in healthier eating behaviors and increased physical activity/exercise, enhanced research on psychosocial determinants of those behavioral changes is needed. Intervention foci on self-regulation have been suggested, but targeted research is required. Method : Women with obesity participated in community-based treatments that were either self-regulation-focused (self-regulation emphasis group; n  = 52) or typical instruction-based (education [treatment-as-usual] group; n  = 54). Results : There were overall significant increases in exercise-related self-regulation, physical activity/exercise, exercise-related self-efficacy, and eating-related self-regulation that were each significantly more pronounced in the self-regulation emphasis group. Increase in exercise-related self-regulation over 3 months predicted eating-related self-regulation over 6 months; however, sequential entry of changes in physical activity and exercise-related self-efficacy significantly mediated that relationship. However, only the path from changes in exercise-related self-regulation to exercise self-efficacy to eating-related self-regulation was significant. In a revised model where change in exercise self-efficacy was the sole mediator, treatment group did not significantly moderate the exercise self-regulation to eating self-regulation change relationship, but full mediation of that relationship occurred. Conclusion : Findings indicated salience for perceived ability/self-efficacy for physical activity, over actual physical activity progress, and its role in the transfer of self-regulatory skills from an exercise to eating context. Increased eating self-regulation significantly predicted weight loss over 6, 12, and 24 months. In the self-regulation emphasis group that translated to meaningful weight loss/weight-loss maintenance of greater than 5% of initial weight. Findings contributed to an increased understanding of psychosocial-change processes within obesity treatment research.

Study Background: Limited knowledge of psychological correlates of weight loss is associated with continuing failures of behavioral obesity treatments beyond the short term., Purpose: This study aimed to inform health professionals' obesity interventions via an increased knowledge of mediators of the exercise-weight loss maintenance relationship., Methods: Women participated in 6-month obesity treatments within community settings emphasizing moderate exercise and self-regulation skills development via primarily in-person ( n  = 54) or primarily written ( n  = 54) means. Changes in mood, self-regulating eating, and weight over 6, 12, and 24 months were assessed. A moderated mediation model was tested using the PROCESS macro instruction., Results: Improvements in mood, self-regulating eating, and weight were significantly greater in the in-person group. The relationship between a dichotomous measure of completing at least 3 sessions of exercise per week (or not) and change in weight over 6 months was no longer significant when the mediators of changes in negative mood and self-regulation of eating were sequentially entered. Paths of exercise→negative mood reduction→eating self-regulation increase→weight loss over 6, 12 and 24 months were significant. Exercise self-regulation at Month 3 significantly moderated the mood change→eating self-regulation change relationship., Conclusions: Based on the identified paths, scalable obesity-treatment content and emphases were informed. This could help guide health professionals' actions concerning the management of obesity., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In most patients with advanced prostate cancer treated with hormonal therapy, androgen independence eventually emerges, leading to death. Androgen receptor signalling remains an important prostate cancer driver, even in the advanced disease stage. MicroRNAs (miRs), non-coding RNAs that regulate gene expression by inhibiting translation and/or promoting degradation of target mRNAs, can act as tumour suppressors or "oncomiRs" and modulate tumour growth. Because of their stability in tissues and in circulation, and their specificity, microRNAs have emerged as potential biomarkers, as well as therapeutic targets in cancer. We identified miR-1271-5p as an androgen receptor modulatory microRNA and we show it can promote hormone sensitive prostate cancer cell growth. Inhibition or overexpression of miR-1271-5p levels affects prostate cancer cell growth, apoptosis and expression of both androgen receptor target genes and other genes that are likely direct targets, dependent on androgen receptor status, and tumour stage. We conclude that miR-1271-5p has the potential to drive progression of hormone-dependent disease and that the use of specific inhibitors of miR-1271-5p may have therapeutic potential in prostate cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kalofonou, Leach, Powell, Waxman, Fletcher and Bevan.)

Issue Addressed: Obesity is an increasing worldwide health issue. In affluent English-speaking countries, obesity ranges from ~28% (Australia) to ~42% (United States) of the adult population. Enabling weight loss beyond an initial 6 months is an unresolved challenge., Methods: Women with obesity participated in community-based obesity treatments incorporating either cognitive-behavioural methods emphasizing self-regulatory skills development (n = 106) or typical information/education processes (n = 47). Psychosocial, behavioural, and weight changes were measured., Results: Significant overall improvements in exercise-related self-regulation and self-efficacy, mood, physical activity/exercise (PA/exercise), diet, and weight were found from baseline-month 6 (weight-loss phase) and baseline-month 12, but not from months 6-12 (weight-loss maintenance phase). Significantly greater improvements were found in the cognitive-behavioural group. Within the weight-loss phase, changes in both PA/exercise and diet significantly contributed to the explained variance in weight loss, whereas within the weight-loss maintenance phase, only change in PA/exercise was a significant predictor. There was no significant relationship of weight loss across phases. Months 6-12 change in PA/exercise significantly mediated relationships of changes in self-regulation→weight, mood→weight, and self-efficacy→weight. Earlier scores and score changes in mood and self-efficacy significantly impacted the subsequent parallel relationships., Conclusions: Cognitive-behavioural methods affect psychosocial changes leading to initial changes in diet, PA/exercise, and weight. Those changes then impact subsequent changes in PA/exercise-a primary malleable correlate of maintained weight loss. SO WHAT?: This research extended previous findings to better-inform behavioural obesity-treatment foci to address the pervasive public health problem of attaining and sustaining weight loss. Findings related to PA/exercise will help impact health-promotion outcomes., (© 2024 Australian Health Promotion Association.)

Extracellular vesicles (EVs) carry diverse biomolecules derived from their parental cells, making their components excellent biomarker candidates. However, purifying EVs is a major hurdle in biomarker discovery since current methods require large amounts of samples, are time-consuming and typically have poor reproducibility. Here we describe a simple, fast, and sensitive EV fractionation method using size exclusion chromatography (SEC) on a fast protein liquid chromatography (FPLC) system. Our method uses a Superose 6 Increase 5/150, which has a bed volume of 2.9 mL. The FPLC system and small column size enable reproducible separation of only 50 µL of human plasma in 15 min. To demonstrate the utility of our method, we used longitudinal samples from a group of individuals who underwent intense exercise. A total of 838 proteins were identified, of which, 261 were previously characterized as EV proteins, including classical markers, such as cluster of differentiation (CD)9 and CD81. Quantitative analysis showed low technical variability with correlation coefficients greater than 0.9 between replicates. The analysis captured differences in relevant EV proteins involved in response to physical activity. Our method enables fast and sensitive fractionation of plasma EVs with low variability, which will facilitate biomarker studies in large clinical cohorts., (© 2024 Battelle Memorial Institute. PROTEOMICS published by Wiley‐VCH GmbH.)

Obesity in the United States has risen to 42 percent of its adult population and is similarly problematic in many other countries. Although the U.S. government has provided education on healthy eating and the need to exercise regularly, behavioral obesity treatments have largely failed to sustain reductions in weight. Self-regulation, and the incorporation of exercise for its psychological impacts on eating, has sometimes been targeted. While there has been sporadic investigation into the carry-over of exercise-related self-regulation to eating-related self-regulation, the present aim is to further inquiry in that area to inform future treatment content for improved effects. Women enrolled in community-based obesity treatments with either a self-regulation ( n  = 106) or education ( n  = 54) focus were assessed on changes in exercise- and eating-related self-regulation, negative mood, completed exercise, and weight. Improvements were significantly greater in the self-regulation-focused group. After controlling for initial change in eating-related self-regulation, change in that measure from Month 3 to 6 was significantly predicted by change in exercise-related self-regulation during the initial 3 treatment months. This suggested a carry-over effect. A stronger predictive relationship was associated with the self-regulation-focused treatment. In further analyses, paths from changes in exercise→negative mood→self-regulation of both exercise and eating were significant. Increase in eating-related self-regulation was significantly associated with weight loss over 6, 12, and 24 months. The self-regulation-focused group had stronger relationships, again. Findings suggested utility in targeting exercise-related self-regulation to impact later change in eating-related self-regulation, and the use of exercise-associated mood improvement to bolster participants' self-regulation capabilities.

Background: Behavioral obesity treatments are typically unable to facilitate meaningful weight loss beyond the short term. Implications of malleable psychosocial factors are unclear, which limits behavioral intervention contents. The current aim was to inform obesity treatments to improve their foci on psychosocial factors leading to resilient behavioral changes and maintained weight loss., Method: Based on pre-planned analyses, women participating in a community-based obesity treatment emphasizing self-regulation and exercise, and who lost at least 3% of their initial weight (N = 89), were measured on eating-related self-efficacy, negative mood, emotional eating, body satisfaction, and self-regulating eating at baseline, Month 3, and Month 6; and on weight change over 12 months., Results: From baseline to Month 6, there was a significant overall improvement in each psychosocial variable. In separate multiple regression equations, scores at (1) Month 6, (2) change from baseline to Month 6, and (3) change from Month 3 to Month 6 were entered as predictors of maintained weight loss from Month 6 to Month 12. Using a backward elimination process, only negative mood was retained in the final Month 6 model, and significantly predicted maintained weight loss (R 2 adjusted  = .03, p = .050). Changes in self-efficacy, mood, emotional eating, and self-regulation were retained in the final baseline to Month 6 model, and significantly predicted weight loss maintained over 12 months (R 2 adjusted  = .30, p < .001)., Conclusion: Findings add to research on obesity treatment development by suggesting an enhanced focus on facilitating changes in self-efficacy, mood, emotional eating, and self-regulation may enhance maintenance of lost weight (or increase weight loss)., (© 2024. International Society of Behavioral Medicine.)

Background: The quantification of microbes, particularly live bacteria, is of utmost importance in assessing the quality of meat products. In the context of meat processing facilities, prompt identification and removal of contaminated carcasses or surfaces is crucial to ensuring the continuous production of safe meat for human consumption. The plate count method and other traditional detection methods are not only labour-intensive but also time-consuming taking 24-48 h., Results: In this report, we present a novel isotachophoretic quantification method utilizing two nucleic acid stains, SYTO9 and propionic iodide, for the detection of total viable bacteria. The study employed E. coli M23 bacteria as a model organism, with an analysis time of only 30 min. The method demonstrated a limit of detection (LOD) of 184 CFU mL -1 and 14 cells mL -1 for total viable count and total cell count, respectively. Furthermore, this new approach is capable of detecting the microbial quality standard limits for food contacting surfaces (10 CFU cm -2 ) and meat (1.99 × 10 4  CFU cm -2 ) by swabbing an area of 10 × 10 cm 2 ., Significance: In contrast to the culture-based methods usually employed in food processing facilities, this isotachophoretic technique enables easy and rapid detection (<30 min) of microorganisms, facilitating crucial decision-making essential for maintaining product quality and safety., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael Breadmore reports financial support was provided by Australian Meat Processor Corporation. Shane Powell reports financial support was provided by Australian Meat Processor Corporation. Michael Breadmore serves as an editor on ACA. Thisara Kumarajithdeclares no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A better understanding of treatment progression and recovery in pulmonary tuberculosis (TB) infectious disease is crucial. This study analyzed longitudinal serum samples from pulmonary TB patients undergoing interventional treatment to identify surrogate markers for TB-related outcomes., Methods: Serum that was collected at baseline and 8, 17, 26, and 52 weeks from 30 TB patients experiencing durable cure were evaluated and compared using a sensitive LC-MS/MS proteomic platform for the detection and quantification of differential host protein signatures relative to timepoint. The global proteome signature was analyzed for statistical differences across the time course and between disease severity and treatment groups., Results: A total of 676 proteins showed differential expression in the serum over these timepoints relative to baseline. Comparisons to understand serum protein dynamics at 8 weeks, treatment endpoints at 17 and 26 weeks, and post-treatment at 52 weeks were performed. The largest protein abundance changes were observed at 8 weeks as the initial effects of antibiotic treatment strongly impacted inflammatory and immune modulated responses. However, the largest number of proteome changes was observed at the end of treatment time points 17 and 26 weeks respectively. Post-treatment 52-week results showed an abatement of differential proteome signatures from end of treatment, though interestingly those proteins uniquely significant at post-treatment were almost exclusively downregulated. Patients were additionally stratified based upon disease severity and compared across all timepoints, identifying 461 discriminating proteome signatures. These proteome signatures collapsed into discrete expression profiles with distinct pathways across immune activation and signaling, hemostasis, and metabolism annotations. Insulin-like growth factor (IGF) and Integrin signaling maintained a severity signature through 52 weeks, implying an intrinsic disease severity signature well into the post-treatment timeframe., Conclusion: Previous proteome studies have primarily focused on the 8-week timepoint in relation to culture conversion status. While this study confirms previous observations, it also highlights some differences. The inclusion of additional end of treatment and post-treatment time points offers a more comprehensive assessment of treatment progression within the serum proteome. Examining the expression dynamics at these later time periods will help in the investigation of relapse patients and has provided indicative markers of response and recovery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Powell 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.)

Background: Although mechanisms are unclear, there is a robust association between exercise and mood improvements. However, beyond ~ 6 months of expected weight loss, weight-management behaviors such as exercise wane as weight gradually regains in most adults. The amount of exercise required to maintain mood improvement is unknown, as is the possible role of theory-based psychosocial changes associated with treatment such as in self-efficacy., Methods: Women who volunteered for a community-based cognitive-behavioral obesity treatment emphasizing exercise and building self-efficacy via self-regulating through lifestyle challenges/barriers, and were of the 86% who reduced their negative mood during its initial 6 months, were allocated into groups who either maintained their negative mood reduction (Sustain group, n = 43) or reverted toward initial levels of negative mood (Revert group, n = 73) during months 6-24. A binary stepwise logistic regression analysis assessed whether exercise amount and/or change in self-efficacy significantly classified Sustain vs. Revert group membership., Results: Change in exercise amount was not significantly associated with group membership. However, after additional entry of change in exercise self-efficacy, a significant association was found - successfully classifying 70% and 42% of the Revert and Sustain group participants, respectively. When self-efficacy change was entered as the sole independent variable, group membership was classified with 62% accuracy, overall (96% in the Revert group)., Conclusions: Consistent with behavioral explanations of the exercise-mood change relationship, it was interpreted that self-efficacy, rather than exercise amount, was an important correlate of mood change beyond month 6. Suggestions for bolstering self-efficacy later in behavioral obesity treatments were provided., (© 2023. International Society of Behavioral Medicine.)

Safety and the quality of products rely on proper cleanliness procedures and good manufacturing practices in the production environment. The use of swabs for the collection of samples from surfaces has been a common practice in industries, medicine and forensic studies. To accommodate these different purposes, many varieties of swabs have been introduced into the market, and it is important to assess the performance of these swabs before incorporating into an environmental monitoring procedure. The overall effectiveness of a swab is determined by two factors: the number of bacteria that a swab can uptake from a surface and the number of picked-up bacteria the swab can elute into a releasing buffer. This study evaluated the uptake efficiency and release efficiency of four different commercially available swabs: CleanFoam (Texwipes, USA), FLOQSwabs (Copan diagnostic Inc., USA), Hydraflock swabs (Puritan medical products, USA), and Cotton swabs. Cotton swabs showed the highest uptake efficiency (96.5 ± 1.9%), whereas CleanFoam swabs (57.9 ± 20.3%) showed the least. Both flocked (FLOQSwabs and Hydraflock) swabs showed over 80% uptake efficiency. Releasing efficiency of swabs was tested with eight different releasing buffers. Cotton swabs displayed the lowest release efficiency with most of the tested releasing buffers. When employed with Tris HEPES, Tris MOPS, Tris TAPS, FLOQSwabs, and Hydraflock swabs exhibited releasing efficiency of over 75%. The overall efficiency of the swabs was determined using TAPS as the releasing buffer and the values obtained were 80.4 ± 9.8%, 54.7 ± 16.9%, 35.0 ± 12.7% and 25.2 ± 6.9% for Hydraflock swabs, FLOQSwabs, Cotton swabs and Cleanfoam swabs, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Intuitive eating (IE) principles present an evidence-based strategy for improving one's relationship with food while reducing the incidence of weight cycling and health risks associated with chronic dieting and weight regain. Offering online programming provides improved access to education while reducing barriers to programme enrollment but is also associated with high rates of attrition. Aim: To examine the process of programme implementation and identify barriers and facilitators of engagement for an online IE programme for employees at a large Midwestern university. Methods: The web-based programme Finding Peace with Food: An Intuitive Eating Approach consisted of an online community with discussion prompts, 10 weekly modules containing videos, activities, and counsellor interviews and was developed using recognized health behaviour theory and evidence-based practices. Participants were university employees (n = 20). Qualitative data were assessed using a phenomenological approach to discern the themes of barriers and facilitators of programme participation. Participation rates were assessed using descriptive statistics. Results: All participants were Caucasian, 85% were female, and their ages ranged from 26-64. The module-based structure was well received. The primary barriers to participation were time constraints, overwhelming amount of information, and aversion to Flipgrid platform use. The quality and usefulness of the programme information were identified as facilitators of participation. Conclusion: Program participation was influenced by the time frame available to complete the programme modules and participants' ease of use of platform applications., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Extracellular vesicles play major roles in cell-to-cell communication and are excellent biomarker candidates. However, studying plasma extracellular vesicles is challenging due to contaminants. Here, we performed a proteomics meta-analysis of public data to refine the plasma EV composition by separating EV proteins and contaminants into different clusters. We obtained two clusters with a total of 1717 proteins that were depleted of known contaminants and enriched in EV markers with independently validated 71% true-positive. These clusters had 133 clusters of differentiation (CD) antigens and were enriched with proteins from cell-to-cell communication and signaling. We compared our data with the proteins deposited in PeptideAtlas, making our refined EV protein list a resource for mechanistic and biomarker studies. As a use case example for this resource, we validated the type 1 diabetes biomarker proplatelet basic protein in EVs and showed that it regulates apoptosis of β cells and macrophages, two key players in the disease development. Our approach provides a refinement of the EV composition and a resource for the scientific community., (© 2023. The Author(s).)

Aconitic acid is an unsaturated tricarboxylic acid that is attractive for its potential use in manufacturing biodegradable and biocompatible polymers, plasticizers, and surfactants. Previously Aspergillus pseudoterreus was engineered as a platform to produce aconitic acid by deleting the cadA (cis-aconitic acid decarboxylase) gene in the itaconic acid biosynthetic pathway. In this study, the aconitic acid transporter gene (aexA) was identified using comparative global discovery proteomics analysis between the wild-type and cadA deletion strains. The protein AexA belongs to the Major Facilitator Superfamily (MFS). Deletion of aexA almost abolished aconitic acid secretion, while its overexpression led to a significant increase in aconitic acid production. Transportation of aconitic acid across the plasma membrane is a key limiting step in its production. In vitro, proteoliposome transport assay further validated AexA's function and substrate specificity. This research provides new approaches to efficiently pinpoint and characterize exporters of fungal organic acids and accelerate metabolic engineering to improve secretion capability and lower the cost of bioproduction., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To improve understanding of psychosocial factors, their changes, and racial differences with implications for behavioral obesity treatments., Methods: Women with obesity of White (n = 64) and Black (n = 33) racial groups participated in cognitive-behavioral community-based obesity treatment and were assessed on body satisfaction, emotional eating, and weight changes over 3, 6, 12, and 24 months via mixed-model repeated-measures analysis of variance and stepwise multiple regression analyses., Results: Baseline body satisfaction scores were significantly higher (P < 0.001) in Black participants. White participants had significantly higher (P = 0.04) emotional eating scores. Significant overall improvements (P < 0.001) in body satisfaction, emotional eating, and weight were found, with weight reduction significantly greater (P = 0.05) among the White women. Weight reductions were significantly predicted by changes in body satisfaction and emotional eating (R 2  = 0.12-0.20, P < 0.01). When racial group was entered into the analyses, the explained variance in weight change over 6 and 12 months significantly increased (P < 0.05)., Conclusions and Implications: Findings suggest addressing body satisfaction, emotional eating, and racial differences by adjusting obesity treatment targets could improve outcomes. Research-to-practice needs include a control group and further identification/elucidation of other psychosocial and economic factors that might affect outcomes., (Copyright © 2023 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Phenylhydroxylamine (PhNHOH) and nitrosobenzene (PhNO) interact with human tetrameric hemoglobin (Hb) to form the nitrosobenzene adduct Hb(PhNO). These interactions also frequently lead to methemoglobin formation in red blood cells. We utilize UV-vis spectroscopy and X-ray crystallography to identify the primary and secondary products that form when PhNHOH and related alkylhydroxylamines (RNHOH; R = Me, t-Bu) react with human ferric Hb. We show that with MeNHOH, the primary product is Hb[α-Fe III (H 2 O)][β-Fe II (MeNO)], in which nitrosomethane is bound to the β subunit but not the α subunit. Attempts to isolate a nitrosochloramphenicol (CAMNO) adduct resulted in our isolation of a Hb[α-Fe II ][β-Fe II -cySOx] {CAMNO} product (cySOx = oxidized cysteine) in which CAMNO was located outside of the protein in the solvent region between the β2 and α2 subunits of the same tetramer. We also observed that the βcys93 residue had been oxidized. In the case of t-BuNHOH, we demonstrate that the isolated product is the β-hemichrome Hb[α-Fe III (H 2 O)][β-Fe III (His) 2 ] {t-BuNHOH} , in which the β heme has slipped ∼4.4 Å towards the solvent exterior to accommodate the bis-His heme coordination. When PhNHOH is used, a similar β-hemichrome Hb[α-Fe III (H 2 O)][β-Fe III (His) 2 -cySOx] {PhNHOH} was obtained. Our results reveal, for the first time, the X-ray structural determination of a β-hemichrome in a human Hb derivative. Our UV-vis and X-ray crystal structural result reveal that although Hb(PhNO) and Hb(RNO) complexes may form as primary products, attempted isolation of these products by crystallization may result in the structural determination of their secondary products which may contain β-hemichromes en route to further protein degradation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ion-sensitive field-effect transistors (ISFETs) in combination with unmodified complementary metal oxide semiconductors present a point-of-care platform for clinical diagnostics and prognostics. This work illustrates the sensitive and specific detection of two circulating mRNA markers for prostate cancer, the androgen receptor and the TMPRSS2-ERG fusion using a target-specific loop-mediated isothermal amplification method. TMPRSS2-ERG and androgen receptor RNA were detected down to 3x10 1 and 5x10 1 copies respectively in under 30 minutes. Administration of these assays onto the ISFET Lab-on-chip device was successful and the specificity of each marker was corroborated with mRNA extracted from prostate cancer cell lines.

Numerous demographic factors have been associated with colorectal cancer (CRC) risk. To better define biological mechanisms underlying these associations, we performed RNA sequencing of stem-cell-enriched organoids derived from the healthy colons of seven European Americans and eight African Americans. A weighted gene co-expression network analysis was performed following RNA sequencing. Module-trait relationships were determined through the association testing of each module and five CRC risk factors (age, body mass index, sex, smoking history, and race). Only modules that displayed a significantly positive correlation for gene significance and module membership were considered for further investigation. In total, 16 modules were associated with known CRC risk factors ( p < 0.05). To contextualize the role of risk modules in CRC, publicly available RNA-sequencing data from TCGA-COAD were downloaded and re-analyzed. Differentially expressed genes identified between tumors and matched normal-adjacent tissue were overlaid across each module. Loci derived from CRC genome-wide association studies were additionally overlaid across modules to identify robust putative targets of risk. Among them, MYBL2 and RXRA represented strong plausible drivers through which cigarette smoking and BMI potentially modulated CRC risk, respectively. In summary, our findings highlight the potential of the colon organoid system in identifying novel CRC risk mechanisms in an ancestrally diverse and cellularly relevant population.

The purpose of this retrospective study was to evaluate the impact of peripherally administered norepinephrine on avoiding central venous catheter insertion while maintaining safety of the infusion. An institutional guideline allows peripheral infusion of norepinephrine via dedicated, 16- to 20-gauge, mid-to-upper arm intravenous (IV) catheters for up to 24 hours. The primary outcome was the need for central venous access in patients initially started on peripherally infused norepinephrine. A total of 124 patients were evaluated (98 initially on peripherally infused norepinephrine vs 26 with central catheter only administration). Thirty-six (37%) of the 98 patients who were started on peripheral norepinephrine avoided the need for central catheter placement, which was associated with $8,900 in direct supply cost avoidance. Eighty (82%) of the 98 patients who started peripherally infused norepinephrine required the vasopressor for ≤12 hours. No extravasation or local complications were observed in any of the 124 patients, regardless of site of infusion. Administration of norepinephrine via a dedicated peripheral IV site appears safe and may lead to a reduction in the need for subsequent central venous access. To achieve timely resuscitation goals, as well as to minimize complications associated with central access, initial peripheral administration should be considered for all patients., Competing Interests: Disclosures: No relevant conflicts of interest to disclose., (Copyright © 2023 Infusion Nurses Society.)

Nitroorganics present a general concern for a safe environment due to their health hazards. However, some nitroorganics such as metronidazole (Mtz) and chloramphenicol (CAM) also possess medicinal value. Mtz and CAM can undergo reductive bioactivation presumably via their nitroso derivatives. We show, using UV-vis spectroscopy, that sperm whale myoglobin (swMb) and its distal pocket mutants retaining H-bonding capacity react with Mtz in the presence of dithionite to generate products with spectra suggestive of the Fe-bound nitroso (Fe-RNO; λ max ~420 nm) forms. We have crystallized and solved the X-ray crystal structure of an H64Q swMb-acetamide compound to 1.76 Å resolution; formation of this compound results from the serendipitous crystallographic trapping, by the heme center, of acetamide from the reductive decomposition of Mtz. Only one of the swMb proteins, namely H64Q swMb with a relatively flexible Gln64 residue, reacted with CAM presumably due to the bulky nature of CAM that generally may restrict its access to the heme site.

Introduction: Lynch syndrome (LS) is a hereditary condition that increases the risk of colorectal (CRC) and extracolonic cancers that exhibit microsatellite instability (MSI-H). MSI-H is driven by defective mismatch repair (dMMR), and approximately 15% of nonhereditary CRCs also exhibit MSI-H. Here, we aimed to better define mechanisms underlying tumor initiation in LS and MSI-H cancers through multi-omic analyses of LS normal colon organoids and MSI-H tumors., Methods: Right (n = 35) and left (n = 23) colon organoids generated from normal colon biopsies at routine colonoscopy of LS and healthy individuals were subjected to Illumina EPIC array. Differentially methylated region (DMR) analysis was performed by DMRcate. RNA-sequencing (n = 16) and bisulfite-sequencing (n = 15) were performed on a subset of right colon organoids. CRISPR-cas9-mediated editing of MMR genes in colon organoids of healthy individuals was followed by quantitative PCR of MSH4. The relationship between MSH4 expression and tumor mutational burden was further explored in three independent tumor data sets., Results: We identified a hypermethylated region of MSH4 in both the right and left colon organoids of LS versus healthy controls, which we validated using bisulfite-sequencing. DMR analysis in three gastrointestinal and one endometrial data set revealed that this region was also hypermethylated in MSI-H versus microsatellite stable (MSS) tumors. MSH4 expression was increased in colon organoids of LS versus healthy subjects and in publicly available MSI-H versus MSS tumors across four RNA-seq and four microarray data sets. CRISPR-cas9 editing of MLH1 and MSH2, but not MSH6, in normal colon organoids significantly increased MSH4 expression. MSH4 expression was significantly associated with tumor mutational burden in three publicly available data sets., Conclusions: Our findings implicate DNA methylation and gene expression differences of MSH4 as a marker of dMMR and as a potential novel biomarker of LS. Our study of LS colon organoids supports the hypothesis that dMMR exists in the colons of LS subjects prior to CRC., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Physical activity (PA) levels among the general population remain low despite well-known benefits. Previous research has demonstrated PA-based charity fundraising events may act as a catalyst for increased motivation for PA by fulfilling basic psychological needs while providing an emotional connection to a greater good. Therefore, the current study used a behavior-change based theoretical paradigm to develop and assess the feasibility of a 12-week charity-based virtual PA program intended to increase motivation and PA adherence. Forty-three participants were enrolled in a virtual 5 K run/walk charity event that included a structured training protocol, web-based motivation resources, and charity education. Eleven participants completed the program and results indicated no differences pre- and post-participation in motivation (t(10) = 1.16, p = .14) and self-efficacy (t(10) = 0.66, p = .26), but increased scores on charity knowledge (t(9) = -2.50, p = .02). Attrition was attributed to timing, weather, and isolated nature of a solo virtual program. Participants enjoyed the structure of the program and felt the training and educational information was beneficial, but could have been more robust. Thus, in its current format, the program design lacks efficacy. Integral changes to increase program feasibility should include group programming, participant-chosen charity, and more accountability., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Our aim is to demonstrate a general-purpose data and knowledge validation approach that enables reproducible metrics for data and knowledge quality and safety. We researched widely accepted statistical process control methods from high-quality, high-safety industries and applied them to pharmacy prescription data being migrated between EHRs. Natural language medication instructions from prescriptions were independently categorized by two terminologists as a first step toward encoding those medication instructions using standardized terminology. Overall, the weighted average of medication instructions that were matched by reviewers was 43%, with strong agreement between reviewers for short instructions (K=0.82) and long instructions (K=0.85), and moderate agreement for medium instructions (K=0.61). Category definitions will be refined in future work to mitigate discrepancies. We recommend incorporating appropriate statistical tests, such as evaluating inter-rater and intra-rater reliability and bivariate comparison of reviewer agreement over an adequate statistical sample, when developing benchmarks for health data and knowledge quality and safety., (©2022 AMIA - All rights reserved.)

The protein artemin acts as both an RNA and protein chaperone and constitutes over 10% of all protein in Artemia cysts during diapause. However, its mechanistic details remain elusive since no high-resolution structure of artemin exists. Here we report the full-length structure of artemin at 2.04 Å resolution. The cryo-EM map contains density for an intramolecular disulfide bond between Cys22-Cys61 and resolves the entire C-terminus extending into the core of the assembled protein cage but in a different configuration than previously hypothesized with molecular modeling. We also provide data supporting the role of C-terminal helix F towards stabilizing the dimer form that is believed to be important for its chaperoning activity. We were able to destabilize this effect by placing a tag at the C-terminus to fully pack the internal cavity and cause limited steric hindrance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Parvate, Powell, Brookreson, Moser, Novikova, Zhou and Evans.)

Prostate cancer (PCa) is the second most common cause of male cancer-related death worldwide. The gold standard of treatment for advanced PCa is androgen deprivation therapy (ADT). However, eventual failure of ADT is common and leads to lethal metastatic castration-resistant PCa. As such, the detection of relevant biomarkers in the blood for drug resistance in metastatic castration-resistant PCa patients could lead to personalized treatment options. mRNA detection is often limited by the low specificity of qPCR assays which are restricted to specialized laboratories. Here, we present a novel reverse-transcription loop-mediated isothermal amplification assay and have demonstrated its capability for sensitive detection of AR-V7 and YAP1 RNA (3 × 10 1 RNA copies per reaction). This work presents a foundation for the detection of circulating mRNA in PCa on a non-invasive lab-on-chip device for use at the point-of-care. This technique was implemented onto a lab-on-chip platform integrating an array of chemical sensors (ion-sensitive field-effect transistors) for real-time detection of RNA. Detection of RNA presence was achieved through the translation of chemical signals into electrical readouts. Validation of this technique was conducted with rapid detection (<15 min) of extracted RNA from prostate cancer cell lines 22Rv1s and DU145s.

Observational studies indicate that calcium supplementation may protect against colorectal cancer. Stratified analyses suggest that this protective effect may differ based on anatomic subsite and sex, but these hypotheses have been difficult to test experimentally. Here, we exposed 36 patient-derived organoid lines derived from normal colon biopsies (21 right colons, 15 left colons) of unrelated subjects (18 female, 18 male) to moderate (1.66 mmol/L) or high (5.0 mmol/L) concentrations of calcium for 72 hours. We performed bulk RNA-sequencing to measure gene expression, and cell composition was inferred using single-cell deconvolution in CIBERSORTx. We tested for significant differences in gene expression using generalized linear models in DESeq2. Exposure to higher levels of calcium was associated with changes in cell composition (P < 0.05), most notably increased goblet and reduced stem cell populations, and differential expression of 485 genes (FDR < 0.05). We found that 40 of these differentially expressed genes mapped to genomic loci identified through colorectal cancer genome-wide association studies, suggesting a potential biologic overlap between calcium supplementation and inherited colorectal cancer risk. Stratified analyses identified more differentially expressed genes in colon organoids derived from right sided colon and male subjects than those derived from left sided colon and female subjects. We confirmed the presence of a stronger right-sided effect for one of these genes, HSD17B2 using qPCR in a subset of matched right and left colon organoids (n = 4). By relating our findings to genetic data, we provide new insights into how nutritional and genetic factors may interact to influence colorectal cancer risk., Prevention Relevance: A chemopreventive role for calcium in colorectal cancer is still unclear. Here, we identify mechanisms through which calcium supplementation may reduce risk. Calcium supplementation increased differentiation and altered expression of colorectal cancer-related genes in a large study of patient-derived colon organoids. These findings were influenced by colon location and sex., (©2022 The Authors; Published by the American Association for Cancer Research.)

Early onset colorectal cancer (EOCRC) rates have increased in recent decades. While lowering the recommended age for routine colonoscopies to 45 may reduce this burden, such measures do not address those who develop CRC before that age. Additional measures are needed to identify individuals at-risk for CRC. To better define transcriptomic events that precede the development of CRC, we performed RNA-sequencing analysis in colon organoids derived from seven healthy and six familial adenomatous polyposis (FAP) patients. This led to the identification of 2635 significant differentially expressed genes (FDR < 0.05). Through secondary analysis of publicly available datasets, we found that these genes were enriched for significant genes also present in FAP CRC and non-hereditary CRC datasets, including a subset that were unique to EOCRC. By exposing FAP colon organoids to a three-day ethanol treatment, we found that two EOCRC-relevant genes were also targets of CRC related lifestyle factors. Our data provides unique insight into the potential, early mechanisms of CRC development in colon epithelial cells, which may provide biomarkers for patient monitoring. We also show how modifiable lifestyle factors may further alter genes relevant to EOCRC, adding weight to the hypothesis that such factors represent an important contributor to increased EOCRC incidence.

Background: Familial adenomatous polyposis (FAP) is an inherited colorectal cancer (CRC) syndrome resulting from germ line mutations in the adenomatous polyposis coli (APC) gene. While FAP accounts for less than 1% of all CRC cases, loss of APC expression is seen in > 80% of non-hereditary CRCs. To better understand molecular mechanisms underlying APC-driven CRC, we performed an epigenome-wide analysis of colon organoids derived from normal-appearing colons of FAP patients versus healthy subjects to identify differentially methylated regions (DMRs) that may precede the onset of CRC., Results: We identified 358 DMRs when comparing colon organoids of FAP patients to those of healthy subjects (FDR < 0.05, |mean beta difference| = 5%). Of these, nearly 50% of DMRs were also differentially methylated in at least one of three CRC tumor and normal adjacent tissue (NAT) cohorts (TCGA-COAD, GSE193535 and ColoCare). Moreover, 27 of the DMRs mapped to CRC genome-wide association study (GWAS) loci. We provide evidence suggesting that some of these DMRs led to significant differences in gene expression of adjacent genes using quantitative PCR. For example, we identified significantly greater expression of five genes: Kazal-type serine peptidase inhibitor domain 1 (KAZALD1, P = 0.032), F-Box and leucine-rich repeat protein 8 (FBXL8, P = 0.036), TRIM31 antisense RNA 1 (TRIM31-AS1, P = 0.036), Fas apoptotic inhibitory molecule 2 (FAIM2, P = 0.049) and (Collagen beta (1-0)galactosyltransferase 2 (COLGALT2, P = 0.049). Importantly, both FBXL8 and TRIM31-AS1 were also significantly differentially expressed in TCGA-COAD tumor versus matched NAT, supporting a role for these genes in CRC tumor development., Conclusions: We performed the first DNA methylome-wide analysis of normal colon organoids derived from FAP patients compared to those of healthy subjects. Our results reveal that normal colon organoids from FAP patients exhibit extensive epigenetic differences compared to those of healthy subjects that appear similar to those exhibited in CRC tumor. Our analyses therefore identify DMRs and candidate target genes that are potentially important in CRC tumor development in FAP, with potential implications for non-hereditary CRC., (© 2022. The Author(s).)

Indonesian salted-boiled fish (pindang) is a popular traditional food in Indonesia, which is made from Scombroid fish such as tuna and mackerel. As with other traditionally prepared fish products, pindang has important economic and social values, especially for those living in the coastal areas of Indonesia. However, pindang is a major cause of histamine fish poisoning (HFP) for consumers. Klebsiella aerogenes T124, a relatively high histamine-producing isolate from pindang, was used to describe lag time (λ), growth rate (μ max ), maximum population density (N max ), and histamine production in histidine broth and artificially contaminated Grey mackerel. Broth was adjusted to 1.5, 6, 10 and 20% w/v NaCl; mackerel was treated with 6% w/w NaCl, a level common to Indonesian industry practice, or not treated with additional NaCl. Samples were incubated at 10, 15, 20 and 30 °C. In broth, μ max and N max were significantly affected by temperature and NaCl, respectively, with λ influenced by both parameters. In control fish, μ max was significantly affected by temperature and NaCl, except at 10 and 15 °C; for 6% NaCl treatment, growth was only observed at 20 and 30 °C. Under similar incubation conditions for broth and fish, histamine formation was markedly affected by NaCl concentration. In broth, -5.1 to -6.6 log μg of histamine was produced per CFU, versus -4.6 to -6.6 log μg per CFU in fish. This study demonstrated that mackerel treated with 6% NaCl and stored at 10-15 °C prevents growth of K. aerogenes strain TI24 and formation of toxic levels of histamine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A frequent limitation of electroporation (EP) and chemical transformation (CT) are the need of tedious and time-consuming procedures for inducing transformation competence, the substantial number of cells required, and the low transformation yields typically achieved. Here, we show a new and rapid electrokinetic method for transformation of small number of noncompetent Escherichia coli TOP10 cells (2-3 × 10 5 ) at room temperature. Escherichia coli TOP10 cells and plasmid DNA are sequentially injected into a 50 μm ID capillary and focused into 11.5 nL by isotachophoresis (ITP) induced by application of high DC voltage (-16 kV). Through ITP, a large excess of plasmid DNA is brought in contact with the cell surface, with the contact time adjusted by application of a counter-pressure (1.3 psi) opposing the ITP movement. The transformation rate was more than 1000-fold higher compared to EP and CT at survival rates greater than 60%., (© 2021 Wiley-VCH GmbH.)

Mechanisms underlying aspirin chemoprevention of colorectal cancer remain unclear. Prior studies have been limited because of the inability of preclinical models to recapitulate human normal colon epithelium or cellular heterogeneity present in mucosal biopsies. To overcome some of these obstacles, we performed in vitro aspirin treatment of colon organoids derived from normal mucosal biopsies to reveal transcriptional networks relevant to aspirin chemoprevention. Colon organoids derived from 38 healthy individuals undergoing endoscopy were treated with 50 μmol/L aspirin or vehicle control for 72 hours and subjected to bulk RNA sequencing. Paired regression analysis using DESeq2 identified differentially expressed genes (DEG) associated with aspirin treatment. Cellular composition was determined using CIBERSORTx. Aspirin treatment was associated with 1,154 significant ( q < 0.10) DEGs prior to deconvolution. We provide replication of these findings in an independent population-based RNA-sequencing dataset of mucosal biopsies (BarcUVa-Seq), where a significant enrichment for overlap of DEGs was observed ( P < 2.2E -16 ). Single-cell deconvolution revealed changes in cell composition, including a decrease in transit-amplifying cells following aspirin treatment ( P = 0.01). Following deconvolution, DEGs included novel putative targets for aspirin such as TRABD2A ( q = 0.055), a negative regulator of Wnt signaling. Weighted gene co-expression network analysis identified 12 significant modules, including two that contained hubs for EGFR and PTGES2 , the latter being previously implicated in aspirin chemoprevention. In summary, aspirin treatment of patient-derived colon organoids using physiologically relevant doses resulted in transcriptome-wide changes that reveal altered cell composition and improved understanding of transcriptional pathways, providing novel insight into its chemopreventive properties. PREVENTION RELEVANCE: Numerous studies have highlighted a role for aspirin in colorectal cancer chemoprevention, though the mechanisms driving this association remain unclear. We addressed this by showing that aspirin treatment of normal colon organoids diminished the transit-amplifying cell population, inhibited prostaglandin synthesis, and dysregulated expression of novel genes implicated in colon tumorigenesis., (©2021 American Association for Cancer Research.)

The electronic or molecular mechanisms that initiate photobiomodulation (PBM) in cells are not yet fully understood. The porcine complex III (C-III) of the electron transport chain was characterized with transient absorption spectroscopy (TAS). We then applied our recently developed continuous wave laser coupled TAS procedure (CW-TAS) to investigate the effect of red light irradiances on the heme dynamics of C-III in its c 1 reduced state. The time constants were found to be 3.3 ± 0.3 ps for vibrational cooling of the oxidized state and 4.9 ± 0.4 ps for rebinding of the photodissociated axial ligand of the c 1 reduced state. The analysis of the CW-TAS procedure yielded no significant changes in the C-III heme dynamics. We rule out the possibility of 635 nm CW light at 4.7 mW/cm 2 inducing a PBM effect on the heme dynamic of C-III, specifically with the photodissociation of its axial ligand., Competing Interests: The authors declare no conflicts of interest., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Tobacco smoke and red/processed meats are well-known risk factors for colorectal cancer (CRC). Most research has focused on studies of normal colon biopsies in epidemiologic studies or treatment of CRC cell lines in vitro . These studies are often constrained by challenges with accuracy of self-report data or, in the case of CRC cell lines, small sample sizes and lack of relationship to normal tissue at risk. In an attempt to address some of these limitations, we performed a 24-hour treatment of a representative carcinogens cocktail in 37 independent organoid lines derived from normal colon biopsies. Machine learning algorithms were applied to bulk RNA-sequencing and revealed cellular composition changes in colon organoids. We identified 738 differentially expressed genes in response to carcinogens exposure. Network analysis identified significantly different modules of co-expression, that included genes related to MSI-H tumor biology, and genes previously implicated in CRC through genome-wide association studies. Our study helps to better define the molecular effects of representative carcinogens from smoking and red/processed meat in normal colon epithelial cells and in the etiology of the MSI-H subtype of CRC, and suggests an overlap between molecular mechanisms involved in inherited and environmental CRC risk., Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to declare., (Copyright: © 2021 Devall et al.)