Exogenous IFN-γ ex vivo shapes the alloreactive T-cell repertoire by inhibition of Th17 responses and generation of functional Foxp3+ regulatory T cells

Interferon (IFN)-γ was originally characterized as a pro-inflammatory cytokine with T helper type 1-inducing activity, but subsequent work has demonstrated that mice deficient in IFN-γ or IFN-γ receptor show exacerbated inflammatory responses and accelerated allograft rejection, suggesting that IFN-γ also has important immunoregulatory functions. Here, we demonstrate that ex vivo IFN-γ conditioning of CD4 T cells driven by allogeneic immature dendritic cells (DC) results in the emergence of a Foxp3+ regulatory T-cell (Treg)- dominant population that can prevent allograft rejection. The development of this population involves conversion of non-Treg precursors, preferential induction of activation-induced cell death within the non-Treg population and suppression of Th2 and Th17 responses. The suppressive activity of IFN-γ is dependent on the transcription factor signal transducer and activator of transcription 1 and is mediated by induced nitric oxide. These data indicate not only how IFN-γ could be used to shape beneficial immune responses ex vivo for possible cell therapy but also provide some mechanistic insights that may be relevant to exacerbated inflammatory responses noted in several autoimmune and transplant models with IFN-γ deficiency

Handling newborn monkeys alters later exploratory, cognitive, and social behaviors

Touch is one of the first senses to develop and one of the earliest modalities for infant-caregiver communication. While studies have explored the benefits of infant touch in terms of physical health and growth, the effects of social touch on infant behavior are relatively unexplored. Here, we investigated the influence of neonatal handling on a variety of domains, including memory, novelty seeking, and social interest, in infant monkeys (Macaca mulatta; n = 48) from 2 to 12 weeks of age. Neonates were randomly assigned to receive extra holding, with or without accompanying face-to-face interactions. Extra-handled infants, compared to standard-reared infants, exhibited less stress-related behavior and more locomotion around a novel environment, faster approach of novel objects, better working memory, and less fear towards a novel social partner. In sum, infants who received more tactile stimulation in the neonatal period subsequently demonstrated more advanced motor, social, and cognitive skills—particularly in contexts involving exploration of novelty—in the first three months of life. These data suggest that social touch may support behavioral development, offering promising possibilities for designing future early interventions, particularly for infants who are at heightened risk for social disorders

Quality circles to improve prescribing patterns in primary medical care: what is their actual impact?

Contains fulltext : 57952.pdf (publisher's version ) (Closed access)RATIONALE, AIMS AND OBJECTIVES: Quality circles comprise small group sessions of doctors and written feedback on their individual practice patterns. Although 50% of German primary care doctors participate in quality circles, their effectiveness has hardly been evaluated in Germany. This study determined the impact of a large-scale programme of quality circles on quality and costs of prescribing. METHOD: A controlled before-after study was performed, in which primary care doctors were allocated to a quality circles group or a control group. Subjects were 100,000 patients in 1996 and in 1998, who had visited one of 177 doctors in the 3 month registration periods in one region in Germany. The intervention comprised a quality circles programme, comprising 11 sessions and repeated feedback on prescribing. Main outcome measures were proportion of patients who received a prescription, mean prescription costs per patient and proportion of generic prescriptions. RESULTS: The absolute numbers of prescriptions decreased in both groups, but the mean prescription costs per patient increased. The quality circles reduced the proportion of patients who received a prescription (OR = 0.86) and the mean prescription costs per patient (B = -3.99 euro), while it increased the proportion of generic drugs (OR = 1.10). The intervention had intended effects on four of the 15 secondary indicators. CONCLUSIONS: Large-scale application of quality circles had intended effects on prescribing decisions in primary care in Germany. The effects found in this study may reflect better what improvements can be achieved than randomized trials of similar interventions