Recent studies highlight the importance of mucins, in particular Muc2, in intestinal homeostasis. Our functional study demonstrates that an alternative secreted mucin, MUC5AC/Muc5ac, is induced in ...colitis to protect the colonic barrier by limiting host-bacterial interaction.
Abstract
Background
The mucus gel layer (MGL) lining the colon is integral to exclusion of bacteria and maintaining intestinal homeostasis in health and disease. Some MGL defects allowing bacteria to directly contact the colonic surface are commonly observed in ulcerative colitis (UC). The major macromolecular component of the colonic MGL is the secreted gel-forming mucin MUC2, whose expression is essential for homeostasis in health. In UC, another gel-forming mucin, MUC5AC, is induced. In mice, Muc5ac is protective during intestinal helminth infection. Here we tested the expression and functional role of MUC5AC/Muc5ac in UC biopsies and murine colitis.
Methods
We measured MUC5AC/Muc5ac expression in UC biopsies and in dextran sulfate sodium (DSS) colitis. We performed DSS colitis in mice deficient in Muc5ac (Muc5ac-/-) to model the potential functional role of Muc5ac in colitis. To assess MGL integrity, we quantified bacterial-epithelial interaction and translocation to mesenteric lymph nodes. Antibiotic treatment and 16S rRNA gene sequencing were performed to directly investigate the role of bacteria in murine colitis.
Results
Colonic MUC5AC/Muc5ac mRNA expression increased significantly in active UC and murine colitis. Muc5ac-/- mice experienced worsened injury and inflammation in DSS colitis compared with control mice. This result was associated with increased bacterial-epithelial contact and translocation to the mesenteric lymph nodes. However, no change in microbial abundance or community composition was noted. Antibiotic treatment normalized colitis severity in Muc5ac-/- mice to that of antibiotic-treated control mice.
Conclusions
MUC5AC/Muc5ac induction in the acutely inflamed colon controls injury by reducing bacterial breach of the MGL.
Blooms of the marine diatom genus Pseudo-nitzschia that produce the neurotoxin domoic acid have been documented with regularity along the coast of southern California since 2003, with the occurrence ...of the toxin in shellfish tissue predating information on domoic acid in the particulate fraction in this region. Domoic acid concentrations in the phytoplankton inhabiting waters off southern California during 2003, 2006, 2007, 2011 and 2017 were comparable to some of the highest values that have been recorded in the literature. Blooms of Pseudo-nitzschia have exhibited strong seasonality, with toxin appearing predominantly in the spring. Year-to-year variability of particulate toxin has been considerable, and observations during 2003, 2006, 2007, 2011 and again in 2017 linked domoic acid in the diets of marine mammals and seabirds to mass mortality events among these animals. This work reviews information collected during the past 15 years documenting the phenology and magnitude of Pseudo-nitzschia abundances and domoic acid within the Southern California Bight. The general oceanographic factors leading to blooms of Pseudo-nitzschia and outbreaks of domoic acid in this region are clear, but subtle factors controlling spatial and interannual variability in bloom magnitude and toxin production remain elusive.
Abstract
Longitudinal virological and serological surveillance is essential for understanding severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) transmission among children but requires ...increased test capacity. We assessed the uptake of serial at-home testing in children (2–17 years) via mailed SARS-CoV-2 antibody and molecular tests. Completion rates demonstrated the feasibility and sustainability of at-home testing across age groups.
Abstract
Background: Background
Neoadjuvant chemoradiotherapy (naCRT) for upper gastrointestinal malignancies induces a pathological complete response (pCR) in 25–85% of patients, depending on ...disease stage and regimen chosen. All patients with a pCR will have a clinical complete response (cCR). Avoidance of surgery is desirable where feasible, as operative intervention entails morbidity and mortality risks and a reduction in lifelong health related quality of life (HRQoL). Pursuant on a policy of permitting selected patients with a cCR to opt for surveillance, this study aims to compare the QoL of patients who chose surveillance over adjuvant surgery following a cCR to naCRT.
Methods: Methods
One hundred and fourteen patients participated in the study. These comprised 4 groups; Group 1 (n = 31) were healthy controls; Group 2 (n = 26) had chemoradiotherapy only; Group 3 (n = 31) had oesophagectomy post naCRT and Group 4(n = 26) had gastrectomy alone. A novel 33 point questionnaire assessing 5 functional domains was completed focusing on symptoms of antro-pyloric function, respiratory reflux and post-vagotomy symptoms, as well as a previously validated questionnaire instrument for purposes of comparison and external validation. The data was aggregated to produce a total score ranging from 20–93 with 20 representing the least symptomatic.
Results: Results
Mean(± sd) overall QoL scores were significantly better in patients avoiding resection (28.9 ± 4.5) vs oesophagectomy (32.3 ± 58. P = 0.042) and vs gastrectomy(33.19 ± 5.9, P = 0.004. Scores did not differ between patients undergoing oesophagectomy or gastrectomy (P = 0.889). Oesophagectomy was associated with a trend towards increased reflux-related respiratory symptoms (7.3 ± 2.2 vs 6.5 ± 1.9; P = 0.396) while gastrectomy patients reported more symptoms related to vagotomy (1.82 ± 0.9 vs 1.4 ± 0.6; P = 0.438) and early dumping (8.2 ± 1.4 vs 7.1 ± 1.7; P = 0.239). The mean score for the control group administered the novel questionnaire was 20.74, approaching the lowest possible score of 20. This was significantly lower than any of the scores recorded for the treatment groups (P = < 0.001).
Conclusion: Discussion
A strategy of active surveillance in complete responders to neoadjuvant chemoradiotherapy is rewarded with a superior quality of life than in those undergoing surgery.
Disclosure
All authors have declared no conflicts of interest.
Abstract
Background
Minorities are often unrepresented in research, which limits equity in healthcare advances. The racial and ethnic disparities in outcomes of individuals infected with COVID-19 ...highlight the importance of inclusivity in research to improve public health measures.
Methods
We performed a descriptive analysis of the racial and ethnic distribution of children enrolled in our COVID-19 Community Research Partnership (CRP) study, a syndromic and serological surveillance study of children aged 2 – 17 years receiving care at three healthcare systems spanning North and South Carolina. Syndromic surveillance involved daily symptom reporting using a web-based monitoring application. Participants consenting to serological surveillance were mailed at-home tests sampling finger prick capillary blood. In-person and electronic recruitment efforts were conducted in English and Spanish. At one of the study sites, we compared the racial/ethnic distribution of enrolled children to the racial/ethnic distribution of all children who received care at the same site during the same timeframe. We compared the racial/ethnic distribution of participants who ultimately submitted samples for serological testing compared to those who consented to serologic testing.
Results
At total of1630 children were enrolled from April 2, 2021 – June 8, 2021. Most children were > 5 years old, 50.2% were female, and 88.5% were from mostly urban counties (Table 1). Of enrolled children, 4.2% were Hispanic, 8.2% were black, and 81.6% were white (Table 2). Among 135,355 unique children who received care at the institution during the same time, 12.4% were Hispanic, 23.0% were black, and 63.1% were white. Of 1552 participants who consented to serologic testing, 4.4% were Hispanic, 8.1% were black, and 81.8% were white (Table 3). To date, 242 children submitted serologic samples; 4.1% were Hispanic, 5.0% were black, and 85.5% were white.
Table 1. Characteristics of enrolled children in COVID-19 surveillance study
Table 2. Racial and Ethnic distribution of children enrolled in the study compared to target population
Table 3. Racial and ethnic distribution of children who participated in serology testing
Conclusion
Despite efforts to recruit a diverse group of children, the proportion of minorities enrolled in our COVID-19 surveillance study underrepresents the targeted population. Ongoing efforts will work to identify barriers and facilitators to research participation among minority families.
Disclosures
Amina Ahmed, MD, Nothing to disclose
Women often stop hormonal contraception because of perceived weight change. We conducted a randomized trial comparing the contraceptive vaginal ring to a low-dose oral contraceptive (OC). We examined ...the difference between women's reported and measured baseline weights and looked at factors affecting perceived weight change.
We randomized 201 participants to either the vaginal ring or an OC for three cycles. We weighed participants upon enrollment (
n=194) and at exit (
n=167), using the same instrument for all measurements. Participants also provided self-reported height and their reactions to perceived weight changes.
Baseline weight and body mass index were similar for both groups (mean weight=145.9 lb). Measured weight was, on average, 4.4 lb more than reported weight; this difference was greater in overweight and obese participants. Participants gained an average of 2.8 lb over 3 months; this gain did not differ between groups or by baseline weight. Subjects who reported a “bad change” in weight at exit (
n=34) gained an average of 4.4 lb, whereas those who reported “no change” (
n=112) gained 2.2 lb and those who reported a “good change” (
n=14) gained 3.3 lb.
Participants underreported their weight, and this difference was greater for heavier women. There was little weight change for the women in our study. Participants' opinions about weight change were not correlated with measured weight changes.
We recruited adolescents to study oral contraceptives versus placebo for dysmenorrhea. We anticipated high discontinuation and concerns about safety, side effects, and sexual behavior. Treatment ...discontinuation (11%) and loss to follow-up (1%) were lower than expected. The most common reason for nonenrollment was logistical issues (63%). Most participants remained abstinent.
Despite the removal of their most reliable clientele and the dire economic situation, architects continued to practice actively in the 1790s, rallying to the challenge of redefining the royal ...patrimony in revolutionary terms. It fell to the Conseil des Bâtiments Civils, architectural arm of the Directory government, to preside over the conversion of ancien-régime space to accommodate a new social agenda. Analyzed here in conjunction with revolutionary legislation, the proceedings of the Conseil's weekly meetings expose significant changes in the nature of architectural work at the close of the eighteenth century.
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