Distinct and Synergistic Contributions of Epithelial Stress and Adaptive Immunity to Functions of Intraepithelial Killer Cells and Active Celiac Disease.

BACKGROUND & AIMS: The mechanisms of tissue destruction during progression of celiac disease are poorly defined. It is not clear how tissue stress and adaptive immunity contribute to the activation of intraepithelial cytotoxic T cells and the development of villous atrophy. We analyzed epithelial cells and intraepithelial cytotoxic T cells in family members of patients with celiac disease, who were without any signs of adaptive antigluten immunity, and in potential celiac disease patients, who have antibodies against tissue transglutaminase 2 in the absence of villous atrophy. METHODS: We collected blood and intestinal biopsy specimens from 268 patients at tertiary medical centers in the United States and Italy from 2004 to 2012. All subjects had normal small intestinal histology. Study groups included healthy individuals with no family history of celiac disease or antibodies against tissue transglutaminase 2 (controls), healthy family members of patients with celiac disease, and potential celiac disease patients. Intraepithelial cytotoxic T cells were isolated and levels of inhibitory and activating natural killer (NK) cells were measured by flow cytometry. Levels of heat shock protein (HSP) and interleukin 15 were measured by immunohistochemistry, and ultrastructural alterations in intestinal epithelial cells (IECs) were assessed by electron microscopy. RESULTS: IECs from subjects with a family history of celiac disease, but not from subjects who already had immunity to gluten, expressed higher levels of HS27, HSP70, and interleukin-15 than controls; their IECs also had ultrastructural alterations. Intraepithelial cytotoxic T cells from relatives of patients with celiac disease expressed higher levels of activating NK receptors than cells from controls, although at lower levels than patients with active celiac disease, and without loss of inhibitory receptors for NK cells. Intraepithelial cytotoxic T cells from potential celiac disease patients failed to up-regulate activating NK receptors. CONCLUSIONS: A significant subset of healthy family members of patients with celiac disease with normal intestinal architecture had epithelial alterations, detectable by immunohistochemistry and electron microscopy. The adaptive immune response to gluten appears to act in synergy with epithelial stress to allow intraepithelial cytotoxic T cells to kill epithelial cells and induce villous atrophy in patients with active celiac disease.

Counseling Women and Couples on Family Planning: A Randomized Study in Jordan.

This article evaluates the effects of involving men in family planning counseling in Jordan using a randomized experiment. We randomly assigned a sample of 1,247 married women to receive women-only counseling, couples counseling, or no counseling. We measured the effects of each type of counseling on family planning use, knowledge, attitudes, and spousal communication about family planning. Compared to no counseling, couples counseling led to a 54 percent increase in uptake of modern methods. This effect is not significantly different from the 46 percent increase in modern method uptake as a result of women-only counseling. This outcome may be due, in part, to lower rates of compliance with the intervention among those assigned to couples counseling compared to women-only counseling. To realize the possible added benefits of involving men, more tailored approaches may be needed to increase men's participation.

Assessment of variables associated with smoking cessation in Crohn's disease.

BACKGROUND: Patients with Crohn's disease (CD) who smoke have a more complicated disease course. AIMS: Our primary objective was to assess smoking related variables that were associated with smoking cessation versus continued smoking in patients with CD. METHODS: A multi-center study identified CD patients who were seen at the University of Chicago and University of Calgary IBD clinics. Patients were categorized into three subgroups: lifetime non-smokers, current smokers, or ex-smokers. Participants completed questionnaires assessing their cigarette smoking behavior. Current smokers were prospectively followed for 6 months to assess smoking status and attempts to quit. Logistic regression analysis was performed to identify factors associated with smoking cessation. RESULTS: Three hundred patients were enrolled with 148 identifying themselves as lifetime non-smokers, 70 as current smokers, and 82 as ex-smokers. Patients who reported their first cigarette within 5 min of waking were more likely to be current smokers (OR = 21; 95% CI 3.94-107.3) as compared to patients who waited greater than 60 min. Current smokers were more likely to have one or more household members who smoked compared to ex-smokers (P < 0.05). Nearly half (49%) of the current smokers were in the precontemplation stage of change (i.e. no intention to quit smoking). At the 6-month follow-up, only 11% reported they quit smoking. CONCLUSIONS: Patients who report a short time to first cigarette in the morning may have more difficulty in smoking cessation. Current smokers were more likely to have another smoker in the household compared to ex-smokers. Current smokers had low levels of motivation to quit smoking and consequently with no intervention, very few quit 6 months after the baseline assessment.

Religious leaders gain ground in the Jordanian family-planning movement.

OBJECTIVE: To assess the effect of a training program designed to enhance the role of Muslim religious leaders (RLs) in promoting family welfare, including reproductive health generally and family planning more specifically. METHODS: A panel study design was utilized; 136 and 115 RLs completed the self-administered questionnaires at baseline (pre-training) and endline (6 months post-training), respectively. Scales were generated to assess RLs' knowledge of the number of family-planning methods deemed to be acceptable according to Islamic teachings (9 methods, Cronbach α=0.85), attitudes toward family planning (7 statements, Cronbach α=0.67), and preaching and/or counseling on family-planning topics (7 topics, Cronbach α=0.85). RESULTS: Linear regressions controlling for sex, age, and educational attainment showed that, on average, RLs cited more methods deemed acceptable according to Islamic teachings (ß=1.381; P<0.001), expressed more positive attitudes toward family planning (ß=0.514; P<0.05), and preached and/or counseled on family-planning topics more frequently at endline compared with baseline (ß=0.965; P<0.01). CONCLUSION: Culturally appropriate training for RLs can lead to a deeper understanding of, and appreciation for, reproductive health and family planning, with the effects manifesting as increased preaching and/or counseling about these important topics.

Client-centered counseling improves client satisfaction with family planning visits: evidence from Irbid, Jordan.

BACKGROUND: High levels of unmet need for family planning and high contraceptive discontinuation rates persist in Jordan, prompting the Jordan Health Communication Partnership (JHCP) to initiate a client-centered family planning service program called "Consult and Choose" (CC), together with community-based activities to encourage women with unmet need to visit health centers. METHODS: We held exit interviews with 461 family planning clients between November-December 2011 to assess, from the clients' perspective, whether trained providers followed the CC protocol and used the CC tools, as well as to measure client satisfaction. We also tracked referral card information from community-based activities to health centers and examined service statistics to explore trends in family planning use. RESULTS: On average, clients reported that providers performed 5.6 of the 7 steps outlined in the CC protocol. Nearly 83% of respondents were very satisfied with their clinic visits. Logistic regression analysis found that the odds of being "very satisfied" increases by 20% with each additional counseling protocol step performed and by 70% with each increase in the number of CC materials used. Between June 2011 and August 2012, 14,490 referral cards from community-based activities were collected in health centers, 59% of which were for family planning services. Service statistic trends indicate an increase in the number of new family planning users and in couple-years of protection after starting the CC program. CONCLUSIONS: Implementation of the CC program at health centers nationally, in tandem with community-based interventions, could play a key role in attaining Jordan's goal of reducing its total fertility rate to 2.1 by 2030. Although this initiative would likely be replicated most readily in other middle-income countries, lower-resource countries could also adapt the tested CC approach.