Effects of supplemental calcium and vitamin D on tight-junction proteins and mucin-12 expression in the normal rectal mucosa of colorectal adenoma patients.

The physical gut barrier, comprised of a thick mucus layer and the epithelium, plays an important role in defense against microbes and foreign antigens. Calcium and vitamin D may be involved in maintaining the integrity of the intestinal mucosal barrier, the dysfunction of which may lead to endotoxemia and inflammation, and contribute to colorectal carcinogenesis. We investigated supplemental calcium (1200 mg, daily) and/or vitamin D3 (1000 IU daily) effects on intestinal barrier function-related biomarkers in a subset of 105 participants from a large colorectal adenoma recurrence chemoprevention clinical trial. We assessed expression of the tight junction proteins claudin-1 (CLDN1), occludin (OCLD), and mucin-12 (MUC12) in the normal-appearing colorectal mucosa using standardized, automated immunohistochemistry and quantitative image analysis. Following 1 year of treatment, in the calcium relative to the no calcium group, the CLDN1, OCLD, and MUC12 expression increased by 14% (P = 0.17), 23% (P = 0.11), and 22% (P = 0.07), respectively. In secondary analyses, the estimated calcium treatment effects were greater among participants with baseline serum 25-OH-vitamin D concentrations below the median value of 22.69 ng/mL (CLDN1: 29%, P = 0.04; OCLD: 36%, P = 0.06; MUC12: 35%, P = 0.05). There were no biomarker expression changes in the vitamin D3 alone group; however, modest increases were found in the combined calcium/vitamin D3 group. At baseline, obesity, history of a sessile-serrated adenoma, colorectal MIB-1/Ki-67 expression, and a family history of colorectal cancer were associated with CLDN1, OCLD, and MUC12 expression. Our study supports continued investigation of factors that could affect intestinal mucosal barrier integrity relevant to colorectal carcinogenesis.

Causes, characteristics, and patterns of prolonged unplanned school closures prior to the COVID-19 pandemic-United States, 2011-2019.

INTRODUCTION: Outside of pandemics, there is little information about occurrence of prolonged unplanned K-12 school closures (PUSC). We describe here the reasons, characteristics, and patterns of PUSC in the United States during 8 consecutive inter-pandemic academic years, 2011-2019. METHODS: From August 1, 2011 through June 30, 2019, daily systematic online searches were conducted to collect data on publicly announced unplanned school closures lasting ≥1 school days in the United States. Closures were categorized as prolonged when schools were closed for ≥5 unplanned days (approximating one full workweek), excluding weekends and scheduled days off per school calendars. RESULTS: During the eight academic years, a total of 22,112 PUSCs were identified, affecting over 800,000 teachers and 13 million students that resulted in 91.5 million student-days lost. A median of 62.9% of students in PUSC-affected schools were eligible for subsidized school meals. Most affected schools were in cities (35%) and suburban areas (33%). Natural disasters (47%), adverse weather conditions (35%), and budget/teacher strikes (15%) were the most frequently cited reasons for PUSC; illness accounted for 1%, and building/facility issues, environmental issues and violence together accounted for the remaining 2%. The highest number of PUSCs occurred in Health and Human Services Regions 2, 3, 4, and 6 encompassing areas that are frequently in the path of hurricanes and tropical storms. The majority of PUSCs in these regions were attributed to a handful of hurricanes during the fall season, including hurricanes Sandy, Irma, Harvey, Florence, and Matthew. CONCLUSIONS: PUSCs occur annually in the United States due to a variety of causes and are associated with a substantive loss of student-days for in-school learning. Both these prior experiences with PUSCs and those during the current COVID-19 pandemic illustrate a need for creating sustainable solutions for high-quality distance learning and innovative supplemental feeding programs nationwide, especially in disaster-prone areas.

Effects of Supplemental Calcium and Vitamin D on Expression of Toll-Like Receptors and Phospho-IKKα/ß in the Normal Rectal Mucosa of Colorectal Adenoma Patients.

Chronic inflammation in the colorectum, a significant contributor to colorectal carcinogenesis, can be triggered by the activation of proinflammatory signaling pathways such as those initiated by Toll-like receptors (TLR) and nuclear factor κB (NF-κB). Although experimental evidence supports calcium and vitamin D potentially modifying these proinflammatory pathways in the colorectum, human data in these regards are scarce. We investigated supplemental calcium (1,200 mg daily) and/or vitamin D3 (1,000 IU daily) effects on inflammatory signaling pathway-related biomarkers in a subset of 105 participants from a colorectal adenoma recurrence chemoprevention clinical trial. We assessed expression of TLR4 and TLR5, which recognize the bacterial components lipopolysaccharides and flagellin, respectively, and phospho-IKKα/ß (pIKKα/ß), a biomarker of inflammation, in the normal-appearing rectal crypt epithelium and stroma using standardized, automated immunohistochemistry and quantitative image analysis. Following 1 year of treatment, TLR4, TLR5, and pIKKα/ß expression in the rectal mucosa did not statistically significantly change with vitamin D or calcium supplementation, taken alone or in combination. Several baseline participant characteristics, including body mass index, history of sessile serrated adenomas, high red/processed meat intake, and high levels of rectal epithelial cell proliferation (as measured by MIB-1/Ki-67), were associated with higher baseline expression of TLRs or pIKKα/ß. Our findings suggest that vitamin D and calcium may have no substantial effect on the investigated biomarkers. However, several modifiable lifestyle factors may be associated with TLRs and pIKKα/ß expression in the normal rectal mucosa, supporting their future investigation as potentially treatable, preneoplastic risk factors for colorectal neoplasms. Cancer Prev Res; 11(11); 707-16. ©2018 AACR.