Increased epithelial cell proliferation in the ileal pouch mucosa of patients with familial adenomatous polyposis

To eliminate the risk of colorectal cancer in patients with familial adenomatous polyposis (FAP), reconstructive proctocolectomy is performed. Although most colonic mucosa is resected during the ileal pouch anal anastomosis, adenomas and carcinomas may develop in the pouch. This may be caused by altered cell kinetics due to intraluminal changes in the pouch. In 32 patients with FAP, biopsy specimens from the mucosa of the pouch and also of the afferent ileal loop were taken. Tissue sections were immunohistochemically processed with the monoclonal antibodies M30 and MIB-1 to assess apoptotic and proliferative indices, respectively. Cell proliferation was also assessed by a modified sign test. There were no significant differences in apoptotic rates between the mucosa of the pouch and the mucosa of the afferent ileal loop. However, cell proliferation was significantly higher in the mucosa of the pouch vs afferent ileal loop, both by using the quantitative (68.3% vs 61.6%, p = 0.001) and semiquantitative methods (p < 0.05). Our newly developed semiquantitative approach outperformed previously described methods. The higher cell proliferation in the pouch as compared to the afferent ileal loop may contribute to the increased risk for adenomas and carcinomas in the pouch of patients with FAP and emphasizes the need for regular endoscopic surveillance

Effects of intervention with sulindac and inulin/VSL#3 on mucosal and luminal factors in the pouch of patients with familial adenomatous polyposis

Contains fulltext : 97862.pdf (publisher's version ) (Open Access)BACKGROUND/AIM: In order to define future chemoprevention strategies for adenomas or carcinomas in the pouch of patients with familial adenomatous polyposis (FAP), a 4-weeks intervention with (1) sulindac, (2) inulin/VSL#3, and (3) sulindac/inulin/VSL#3 was performed on 17 patients with FAP in a single center intervention study. Primary endpoints were the risk parameters cell proliferation and glutathione S-transferase (GST) detoxification capacity in the pouch mucosa; secondary endpoints were the short chain fatty acid (SCFA) contents, pH, and cytotoxicity of fecal water. METHODS: Before the start and at the end of each 4-week intervention period, six biopsies of the pouch were taken and feces was collected during 24 h. Cell proliferation and GST enzyme activity was assessed in the biopsies and pH, SCFA contents, and cytotoxicity were assessed in the fecal water fraction. The three interventions (sulindac, inulin/VSL#3, sulindac/inulin/VSL#3) were compared with the Mann-Whitney U test. RESULTS: Cell proliferation was lower after sulindac or VSL#3/inulin, the combination treatment with sulindac/inulin/VSL#3 showed the opposite. GST enzyme activity was increased after sulindac or VSL#3/inulin, the combination treatment showed the opposite effect. However, no significance was reached in all these measures. Cytotoxicity, pH, and SCFA content of fecal water showed no differences at all among the three treatment groups. CONCLUSION: Our study revealed non-significant decreased cell proliferation and increased detoxification capacity after treatment with sulindac or VSL#3/inulin; however, combining both regimens did not show an additional effect

Planning and Designing Walkable Cities: A Smart Approach

Walking may be considered one of the most sustainable and democratic ways of travelling within a city, thus providing benefits not only to pedestrians but also to the urban environment. Besides, walking is also one of the means of transport most likely subjected to factors outside an individual\u2019s control, like social or physical abilities to walk and the presence of comfortable and safe street infrastructures and services. Therefore, improving urban conditions provided to pedestrians has positive impacts on walkability. At the same time technological solutions and innovations have the power to encourage and support people to walk by overcoming immaterial barriers due to a lack of information or boring travel and they give to decision makers the possibility to gain data to understand how and where people travel. Merging these two dimensions into a unique approach can drastically improve accessibility, attractiveness, safety, comfort and security of urban spaces. In this context, this paper aims to draw a more multifaceted context for walkability, where new technologies assume a key role for introducing new approaches to pedestrian paths planning and design and thus for enhancing this mode of transport. Indeed, by combining more traditional spatial-based and perceptual analysis of the urban environment with technological applications and social media exploitation there will be room to better support the decision on and to enhance satisfaction of walking as well as to easier plan and design more walkable cities

Online versus in-person comparison of Microscale Audit of Pedestrian Streetscapes (MAPS) assessments: reliability of alternate methods

Abstract Background An online version of the Microscale Audit of Pedestrian Streetscapes (Abbreviated) tool was adapted to virtually audit built environment features supportive of physical activity. The current study assessed inter-rater reliability of MAPS Online between in-person raters and online raters unfamiliar with the regions. Methods In-person and online audits were conducted for a total of 120 quarter-mile routes (60 per site) in Phoenix, AZ and San Diego, CA. Routes in each city included 40 residential origins stratified by walkability and SES, and 20 commercial centers. In-person audits were conducted by raters residing in their region. Online audits were conducted by raters in the alternate location using Google Maps (Aerial and Street View) images. The MAPS Abbreviated Online tool consisted of four sections: overall route, street segments, crossings and cul-de-sacs. Items within each section were grouped into subscales, and inter-rater reliability (ICCs) was assessed for subscales at multiple levels of aggregation. Results Online and in-person audits showed excellent agreement for overall positive microscale (ICC = 0.86, 95% CI [0.80, 0.90]) and grand scores (ICC = 0.93, 95% CI [0.89, 0.95]). Substantial to near-perfect agreement was found for 21 of 30 (70%) subscales, valence, and subsection scores, with ICCs ranging from 0.62, 95% CI [0.50, 0.72] to 0.95, 95% CI [0.93, 0.97]. Lowest agreement was found for the aesthetics and social characteristics scores, with ICCs ranging from 0.07, 95% CI [−0.12, 0.24] to 0.27, 95% CI [0.10, 0.43]. Conclusions Results support use of the MAPS Abbreviated Online tool to reliably assess microscale neighborhood features that support physical activity and may be used by raters residing in different geographic regions and unfamiliar with the audit areas

The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up.

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value \u3c0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for \u3c5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality

Age differences in the association of childhood obesity with area-level and school-level deprivation: cross-classified multilevel analysis of cross-sectional data.

OBJECTIVE: Evidence suggests that area-level deprivation is associated with obesity independently of individual socioeconomic status; however, although the school may also have an impact on child health, few studies have investigated the association between school-level deprivation and the body mass index (BMI) of students. The aim of this study was to assess the relationship between the BMI for children of different ages and area-level and school-level deprivation. SUBJECTS: BMI measurements were collected through the National Child Measurement Programme (NCMP) that samples from two school years: 396,171 reception year pupils (4-5-year olds) and 392,344 year 6 pupils (10-11-year olds) from 14,054 primary schools in England. DESIGN: Cross-classified multilevel models with four levels: individual (n=788,525), lower super output areas corresponding to area of residence (n=29,606), schools (n=14,054) and primary care trusts (PCTs, n=143), which coordinate the collection of data within a large area, were used to study the relationship between measures of deprivation at an area and school level, and childhood BMI within England. RESULTS: A positive association was found between the area and school measures of deprivation, and student BMI. Both the measures of deprivation explained a greater proportion of variance in BMI z-scores for year 6 students than for the reception year students, with a greater difference between the year groups found with the school-level measure of socioeconomic status than for the the area-level measure. CONCLUSIONS: Deprivation explains a greater proportion of the variance in BMI for older compared with younger children, perhaps reflecting the impact of deprivation as children age, highlighting the widening of health inequalities through childhood. The association with school-level deprivation illustrates the impact of the school on BMI status throughout the primary school years