Vstm3 is a member of the CD28 family and an important modulator of T-cell function.

Members of the CD28 family play important roles in regulating T-cell functions and share a common gene structure profile. We have identified VSTM3 as a protein whose gene structure matches that of the other CD28 family members. This protein (also known as TIGIT and WUCAM) has been previously shown to affect immune responses and is expressed on NK cells, activated and memory T cells, and Tregs. The nectin-family proteins CD155 and CD112 serve as counter-structures for VSTM3, and CD155 and CD112 also bind to the activating receptor CD226 on T cells and NK cells. Hence, this group of interacting proteins forms a network of molecules similar to the well-characterized CD28-CTLA-4-CD80-CD86 network. In the same way that soluble CTLA-4 can be used to block T-cell responses, we show that soluble Vstm3 attenuates T-cell responses in vitro and in vivo. Moreover, animals deficient in Vstm3 are more sensitive to autoimmune challenges indicating that this new member of the CD28 family is an important regulator of T-cell responses.

Orlistat accentuates the fat-induced fall in blood pressure in older adults.

Postprandial hypotension may be influenced by the digestion of fat. The aim of the present study was to evaluate the hypothesis that products of fat digestion mediate the hypotensive response to fat. In part A of the study, nine healthy older subjects were studied on three separate occasions in randomised order. Blood pressure, heart rate (HR), plasma TAG and gastric emptying were measured following the ingestion of equivolaemic drinks: (1) 300 ml of high-fat drink (88 % fat); (2) fat drink mixed with 120 mg orlistat (lipase inhibitor); (3) water (control). In part B of the study, ten healthy older subjects were studied on two separate occasions. Blood pressure, HR, plasma TAG and superior mesenteric artery flow were measured during 90 min intraduodenal infusions of 10 % intralipid (2·7 ml/min), with and without 120 mg orlistat. Oral fat ingestion was associated with decreases in systolic and diastolic blood pressures (both P = 0·0001) that were greater when orlistat was co-administered (both P < 0·05), and an increase in HR (P = 0·0001) that was inhibited by orlistat co-administration (P < 0·03). Gastric emptying was slowed by oral fat digestion, and orlistat administration inhibited this slowing (P < 0·04). Intraduodenal fat infusion was not associated with changes in blood pressure but increased HR (P < 0·0001), an effect attenuated by orlistat (P < 0·05). In conclusion, orlistat potentiates the hypotensive response to oral fat in older adults, possibly as a result of faster gastric emptying of fat. The results do not support a role for fat digestion in lowering blood pressure.

Carbohydrate and fat digestion is necessary for maximal suppression of total plasma ghrelin in healthy adults.

It is uncertain whether the postprandial suppression of ghrelin is dependent on digestion and absorption of nutrients or whether the presence of nutrients in the small intestine is sufficient. Twenty-four healthy young adults with a mean age of 23 ± 0.6 years were examined on 3 separate days after an overnight fast. Twelve subjects participated in Part A, and the other 12 subjects in Part B. In Part A, subjects consumed, in random order, one of three study drinks: 300 mL water; 300 mL high-fat drink, with and without, 120 mg orlistat. In Part B, subjects received, in random order, one of three drinks: 300 mL water; 300 mL sucrose, with and without, 100mg acarbose. In both parts gastric emptying as measured by 2-D ultrasound. In Part A, plasma ghrelin concentrations decreased following ingestion of the high-fat drink, but did not change with the high-fat-orlistat drink or water. In Part B, the suppression of plasma ghrelin following the sucrose drink, was attenuated by acarbose. Orlistat accelerated gastric emptying of the high-fat drink, while acarbose delayed gastric emptying of the sucrose drink. In conclusion, fat and carbohydrate digestion is required for maximal suppression of ghrelin secretion.

Assessing the impact of an emotion regulation booster program for elementary school-aged children.

The purpose of this study was to determine whether children who participated in a booster program 3 years after completing an emotion regulation program show a greater increase between pretest and post-test in the development of emotion regulation skills than children in a comparison group. A booster program was implemented as a pilot project with seven children ages 12-14. The contrast group consisted of eight children ages 10-14. Results of the study showed that the booster group had significant increases on 4 of 10 outcome measures: emotional awareness, emotional expressiveness, number of identified body cues, and number of identified calming activities. The contrast group showed no significant pretest post-test changes on the outcomes measured. EDITORS' STRATEGIC IMPLICATIONS: Replication will be required with a larger sample size, but the emotion regulation results presented are encouraging. Program developers and evaluators will benefit from the authors' discussion of the importance and role of booster programs.

Fasting ghrelin is related to skeletal muscle mass in healthy adults.

BACKGROUND/OBJECTIVES: The determinants of plasma ghrelin concentrations including the effects of aging, gender, and body composition, are unclear. Appetite and energy intake decrease with advancing age, and there is a corresponding decline in total body lean tissue, and an increase in fat mass. METHODS: We measured fasting plasma ghrelin and insulin concentrations in 52 healthy subjects aged 22-82 years, and assessed body composition by dual energy X-ray absorptiometry. Energy intake was estimated from diet diaries. RESULTS: Fasting ghrelin concentrations were not significantly correlated with age and energy intake (R = 0.07, P = 0.62; and R = -0.14, P = 0.34 respectively) on univariate regression analysis, and ghrelin concentrations were higher in females than males (2886.8 +/- 182.1 pg/ml vs 2082.5 +/- 121.2 pg/ml; P = 0.001). Ghrelin was inversely related to body mass index (R = -0.328, P = 0.018), fat-free body mass (R = -0.428, P = 0.002), and total skeletal muscle mass (R = -0.439, P = 0.001), but not related to body fat mass (R = 0.177, P = 0.208). On multiple regression analysis, total skeletal muscle mass (corrected for height) was the only significant negative predictor (P < 0.0001) of fasting ghrelin concentrations. CONCLUSIONS: In conclusion, in healthy adults, plasma ghrelin concentrations are not significantly influenced by age or energy intake per se, but relate to skeletal muscle mass.

Effect of testosterone and a nutritional supplement, alone and in combination, on hospital admissions in undernourished older men and women.

BACKGROUND: In older people, undernutrition is associated with increased hospitalization rates and mortality. Because weight loss in older people often reflects a disproportionate reduction of skeletal muscle, anabolic treatments may be beneficial. OBJECTIVE: Our aim was to evaluate the hypothesis that testosterone treatment and a nutritional supplement have additive benefits. DESIGN: Oral testosterone undecanoate (40 mg daily for women, 80 mg twice daily for men) and an oral nutritional supplement (475 kcal/d) were administered, alone or combined, for 1 y to 49 community-dwelling, undernourished people [Mini Nutritional Assessment score <24 and low body weight (body mass index, in kg/m(2): <22) or recent weight loss (>7.5% over 3 mo)] aged >65 y (mean age: 77 y; 26 women and 23 men). Hospital admissions and other variables were assessed. RESULTS: In subjects receiving combined testosterone and nutritional supplements (n = 11), there were no hospital admissions, whereas there were 9 admissions (2 elective) in 13 subjects in the no-treatment group, 4 in the testosterone-treated group (n = 12), and 5 in the supplement-treated group (n = 13); P = 0.06 with no-treatment compared with combined treatment. When compared with the no-treatment group, the combined-treatment group had significantly fewer subjects admitted to hospital (0 compared with 5, P = 0.03), fewer days in hospital (0 compared with 74, P = 0.041), and a longer time to hospital admission (P = 0.017). CONCLUSIONS: In undernourished older people, combined treatment with testosterone and nutritional supplementation reduced the number of people hospitalized and the duration of hospital admissions, which are important endpoints in this group. Larger, confirmatory studies are now needed. This trial was registered before commencement at clinical trials.gov as NCT00117000.

Controlled, open, randomized multicenter trial comparing the effects of treatment on quality of life, safety and efficacy of budesonide foam and betamethasone enemas in patients with active distal ulcerative colitis.

BACKGROUND/AIMS: There is evidence of a higher quality of life with foams as compared with enemas. The purpose of this study was to assess the effect of treatment with budesonide foam or betamethasone enema on the quality of life and the clinical outcome in patients with distal ulcerative colitis. METHODOLOGY: In an open multicenter trial, patients with active distal ulcerative colitis were randomized to receive 2 mg/50 mL budesonide foam or 5 mg/100 mL betamethasone enema. Primary outcome variable was the change in the mean Life Quality Index. Therapeutic efficacy was determined by clinical activity, endoscopical and histological indices. RESULTS: 38 patients were included in the study. The decrease of the mean Life Quality Index was more pronounced in the budesonide group. No significant difference in the efficacy of treatment was observed for both groups. Betamethasone suppressed the plasma cortisol level in the majority of the patients (87%) compared to only 22% of the patients receiving budesonide. CONCLUSIONS: The quality of life is not significantly different in patients during treatment with budesonide foam or betamethasone enema for active distal ulcerative colitis. However, while having comparable clinical efficacy budesonide foam has less effect on the plasma cortisol level thus potentially minimizing steroid side effects.

Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice.

T cell-derived cytokines are important in the development of an effective immune response, but when dysregulated they can promote disease. Here we identify a four-helix bundle cytokine we have called interleukin 31 (IL-31), which is preferentially produced by T helper type 2 cells. IL-31 signals through a receptor composed of IL-31 receptor A and oncostatin M receptor. Expression of IL-31 receptor A and oncostatin M receptor mRNA was induced in activated monocytes, whereas epithelial cells expressed both mRNAs constitutively. Transgenic mice overexpressing IL-31 developed severe pruritus, alopecia and skin lesions. Furthermore, IL-31 receptor expression was increased in diseased tissues derived from an animal model of airway hypersensitivity. These data indicate that IL-31 may be involved in promoting the dermatitis and epithelial responses that characterize allergic and non-allergic diseases.