Deficiency of immunoregulatory indoleamine 2,3-dioxygenase 1in juvenile diabetes.

A defect in indoleamine 2,3-dioxygenase 1 (IDO1), which is responsible for immunoregulatory tryptophan catabolism, impairs development of immune tolerance to autoantigens in NOD mice, a model for human autoimmune type 1 diabetes (T1D). Whether IDO1 function is also defective in T1D is still unknown. We investigated IDO1 function in sera and peripheral blood mononuclear cells (PBMCs) from children with T1D and matched controls. These children were further included in a discovery study to identify SNPs in IDO1 that might modify the risk of T1D. T1D in children was characterized by a remarkable defect in IDO1 function. A common haplotype, associated with dysfunctional IDO1, increased the risk of developing T1D in the discovery and also confirmation studies. In T1D patients sharing such a common IDO1 haplotype, incubation of PBMCs in vitro with tocilizumab (TCZ) - an IL-6 receptor blocker - would, however, rescue IDO1 activity. In an experimental setting with diabetic NOD mice, TCZ was found to restore normoglycemia via IDO1-dependent mechanisms. Thus, functional SNPs of IDO1 are associated with defective tryptophan catabolism in human T1D, and maneuvers aimed at restoring IDO1 function would be therapeutically effective in at least a subgroup of T1D pediatric patients.

First-Person Perspective Action Observation Training in Individuals With Parkinson's Disease: A Consideration-of-Concept Controlled Pilot Trial.

BACKGROUND AND PURPOSE: Action observation training (AOT) consists of the observing of actions performed by others, followed by imitation. Physical therapy techniques based on action observation may influence motor performance in individuals with idiopathic Parkinson's disease (IPD). OBJECTIVES: The aim of this pilot study was to provide a preliminary approach to assess AOT in anatomical first-person perspective (FPP) as a rehabilitation technique to improve body function and activity in individuals with disability due to IPD. METHODS: Videos showing in FPP movements of the upper and lower limbs were produced. A research protocol was designed and tested for feasibility. After baseline assessment, 16 participants with mild to moderate disability due to IPD, all receiving conventional physical therapy group treatment, were nonrandomly assigned to either 1 extra hour of individualized FPP AOT per session or comparison group. Upper and lower limb functioning, independence in activity of daily living, and mobility were assessed before and after training. Data were analyzed by descriptive statistics; statistical comparisons were conducted as part of the feasibility assessment of the data management plan by means of nonparametric tests. RESULTS: A set of 22 videos was created and administered. Groups were comparable at baseline assessment. All participants completed the study and had complete data. Compared with baseline, both groups improved significantly. The experimental group had a better response based on change scores, and the differences were large for 3 of the outcome measures. No significant between-group differences were observed. DISCUSSION: The equipment needed for the production of the videos was easily available. The study protocol was successfully implemented. Adherence rates to study procedures were excellent, and no adverse events occurred. Differences in methods and participant populations prevented comparison in our experimental approach. The number and content of videos, and the length of the sessions proposed, was close to that of other studies providing an FPP AOT program in individuals with cerebral palsy and stroke. Both groups improved and the effect was greater for the experimental one. However, no significant difference between the groups was observed. CONCLUSIONS: This pilot study suggests that FPP AOT is a feasible intervention and the research protocol designed would be suitable, with minor modifications, for the conduction of a subsequent stage 2 trial designed to verify the hypothesis that the adjunct of FPP AOT might improve motor performance in individuals with IPD.

Description of the EUROBIS program: a combination of an Epode community-based and a clinical care intervention to improve the lifestyles of children and adolescents with overweight or obesity.

The present paper describes the Epode Umbria Region Obesity Prevention Study (EUROBIS) and aims to implement the C.U.R.I.A.MO. model through the EPODE methodology. The main goal of the EUROBIS is to change the pendency of slope of the actual trend towards the increase in the yearly rates of childhood overweight and obesity in Umbria and to improve healthy lifestyles of children and their parents. The project is the first EPODE program to be performed in Italy. The aims of the Italian EUROBIS study are: (1) a community-based intervention program (CBP) carrying out activities in all primary schools of the Umbria Region and family settings as first step, to reverse the current obesity trend on a long-term basis, and (2) a clinical care program for childhood and adolescent by C.U.R.I.A.MO. model. C.U.R.I.A.MO. model is a multidisciplinary approach to improve three key aspects of healthy lifestyles: nutrition, exercise, and psychological aspects with the strategy of a family-based approach. The community-based intervention and clinical trial provide an innovative valuable model to address the childhood obesity prevention and treatment in Italy.

Parental alliance and family functioning in pediatric obesity from both parents' perspectives.

OBJECTIVE: The aim of the present study was to investigate the maternal and paternal specific contributions on the associations between family socioeconomic status, parental anthropometric factors, parental alliance, and family functioning. These were assessed separately for mothers and fathers, by means of a case-control study with families of Italian youths with and without overweight/obesity. METHODS: Ninety families with children aged 11 to 16 years (mean = 13.27 years; SD = 1.5) participated in the study. Half of the families included children with overweight/obesity (n = 45). The body mass indices (BMIs) of youths and parents were measured and the former transformed in BMI z-scores. The parents completed the Parenting Alliance Measure and the Family Assessment Measure Version III, General Scale. RESULTS: Higher levels of dysfunction in parental alliance and family functioning of the mothers and fathers of the overweight/obese group were found. Socioeconomic status did not contribute significantly to the prediction of overweight and obesity in youth. Both maternal and paternal BMIs were positively associated with youth overweight/obesity. The degrees of parental alliance perceived by both mothers (odds ratio [OR], 81; 95% confidence interval [CI], 0.72-0.90) and fathers (OR, 89; 95% CI, 0.81-0.98) predicted child's weight status. The perception of poor parental and familial functioning by both parents contributed to the prediction of overweight and obesity in youth (mother: OR, 1.06; 95% CI, 1.02-1.10; father: OR, 1.06; 95% CI, 1.01-1.11). CONCLUSION: The results support a strong effect of parental and family functioning on a youth's overweight/obesity also from the father's perspective. The importance of considering the father's perspective is discussed.

An optimisation approach to multiprobe cryosurgery planning.

In cryosurgery operations, tumoural cells are killed by means of a freezing procedure realised with the insertion of cryoprobes in the diseased tissue. Cryosurgery planning aims at establishing the best values for operation parameters like number and position of the probes or temperature and duration of the freezing process. Here, we present an application of ant colony optimisation (ACO) to cryosurgery planning, whereby the ACO cost function is computed by numerically solving several direct Stefan problems in biological tissues. The method is validated in the case of a 2D phantom of a prostate cross section.

Retrovirus-like long-terminal repeat DQ-LTR13 and genetic susceptibility to type 1 diabetes and autoimmune Addison's disease.

Controversial data are available on the association between the retrovirus-like long-terminal repeat (LTR) DQ-LTR13 and genetic susceptibility to type 1 diabetes and other autoimmune diseases. We analyzed DNA samples from 315 type 1 diabetic patients, 166 autoimmune Addison's disease (AAD) patients, 1,054 healthy subjects, and 144 families of type 1 diabetic offspring. DQ-LTR13 was more frequent among patients than healthy subjects (P(c) < 0.0006), and a preferential transmission of DQB1*0302-LTR13(+) from parents to type 1 diabetic offspring was observed. DQ-LTR13 was in linkage disequilibrium (LD) with DQB1*0302 but not DQB1*0201. The presence of DQ-LTR13 increased the odds ratio of DQB1*0302 2.9- to 3.2-fold for type 1 diabetes and AAD. DRB1*0403 was absent in all of the 169 DRB1*04-positive patients but present in 27% (34 of 127) DRB1*04-positive healthy subjects (P(c) < 0.001). DQ-LTR13 was detected in 1 of 34 (3%) DRB1*0403-positive healthy subjects and 36 of 93 (39%) individuals carrying another DRB1*04 allele (P(c) = 0.002). Multivariate logistic regression analysis revealed that DQ-LTR13 is not independently associated with type 1 diabetes and AAD after correction for DQB1*0302 and DRB1*0403. Conversely, DQB1*0201, DQB1*0302, DRB1*0401, and DRB1*0403 were all significantly associated with disease risk also after correction for DQ-LTR13. We provide conclusive evidence that the genetic association of DQ-LTR13 with type 1 diabetes and AAD is primarily due to a LD with DQB1*0302 and DRB1*0403.