Plasma microRNA ratios associated with breast cancer detection in a nested case-control study from a mammography screening cohort.

Mammographic breast cancer screening is effective in reducing breast cancer mortality. Nevertheless, several limitations are known. Therefore, developing an alternative or complementary non-invasive tool capable of increasing the accuracy of the screening process is highly desirable. The objective of this study was to identify circulating microRNA (miRs) ratios associated with BC in women attending mammography screening. A nested case-control study was conducted within the ANDROMEDA cohort (women of age 46-67 attending BC screening). Pre-diagnostic plasma samples, information on life-styles and common BC risk factors were collected. Small-RNA sequencing was carried out on plasma samples from 65 cases and 66 controls. miR ratios associated with BC were selected by two-sample Wilcoxon test and lasso logistic regression. Subsequent assessment by RT-qPCR of the miRs contained in the selected miR ratios was carried out as a platform validation. To identify the most promising biomarkers, penalised logistic regression was further applied to candidate miR ratios alone, or in combination with non-molecular factors. Small-RNA sequencing yielded 20 candidate miR ratios associated with BC, which were further assessed by RT-qPCR. In the resulting model, penalised logistic regression selected seven miR ratios (miR-199a-3p_let-7a-5p, miR-26b-5p_miR-142-5p, let-7b-5p_miR-19b-3p, miR-101-3p_miR-19b-3p, miR-93-5p_miR-19b-3p, let-7a-5p_miR-22-3p and miR-21-5p_miR-23a-3p), together with body mass index (BMI), menopausal status (MS), the interaction term BMI * MS, life-style score and breast density. The ROC AUC of the model was 0.79 with a sensitivity and specificity of 71.9% and 76.6%, respectively. We identified biomarkers potentially useful for BC screening measured through a widespread and low-cost technique. This is the first study reporting circulating miRs for BC detection in a screening setting. Validation in a wider sample is warranted.Trial registration: The Andromeda prospective cohort study protocol was retrospectively registered on 27-11-2015 (NCT02618538).

Routine vs. On-Demand Discharge Planning Strategy in Intermediate-Risk Patients for Complex Discharge: a Cluster-Randomized, Multiple Crossover Trial.

BACKGROUND: Early hospital discharge planning can help to reduce the length of stay and unplanned readmission in high-risk patients. Therefore, it is important to select patients who can benefit from a personalized discharge planning based on validated tools. The modified Blaylock Risk Assessment Screening Score (BRASS) is routinely used in the Molinette Hospital (Turin, Italy) to screen patients at high risk for discharge, but the effectiveness of the discharge planning is uncertain in intermediate-risk patients. OBJECTIVE: To evaluate the best strategy for discharge planning by the Continuity of Care Hospital Unit (CCHU) in intermediate-risk patients according to modified BRASS. DESIGN: Cluster-randomized, multiple crossover trial. PARTICIPANTS: Adult patients admitted in the Medicine and Neurology departments of the Molinette Hospital in Turin, Italy, between June 2018 and May 2019 with a BRASS intermediate risk. INTERVENTIONS: A routine discharge planning strategy (RDP, Routine Discharge Plan), which involved the management of all intermediate-risk patients, was compared to an on-demand discharge planning strategy (DDP, on-Demand Discharge Planning), which involved only selected patients referred to the CCHU by ward staff. MAIN MEASURES: The primary outcome was the 90-day hospital readmission for any cause (HR90). Secondary outcomes included the prolonged length of stay (pLOS). KEY RESULTS: Eight hundred two patients (median age 79 years) were included (414 RDP and 388 DDP). Comparing RDP vs. DDP periods, HR90 was 27.6% and 27.3% (OR 1.01, 90%CI 0.76-1.33, p = 0.485); and pLOS was 47 (11.4%) and 40 (10.3%) (OR 1.24, 95%CI 0.72-2.13, p = 0.447), respectively. CONCLUSIONS: This is one of the largest randomized study conducted to compare the effectiveness of two different hospital discharge planning strategies. In patients with intermediate risk of hospital discharge, a RDP offers no advantage over a DDP and results in an unnecessary increase in staff workload. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03436940.

The Consensus Project: Participation in cervical cancer screening by the first cohorts of girls offered HPV vaccination at age 15-16 years in Italy.

OBJECTIVE: To evaluate the association between human papillomavirus vaccination status and participation in cervical cancer screening (at age 25) by the first cohorts of girls who were offered vaccination at the age of 15 to 16 years in Italy. METHODS: Women born in 1993, 1994 and 1995 were invited to participate in cervical cancer screening between 2018 and 2020. We report participation in screening by vaccination status in three large areas, Florence province, Piedmont region and Savona province, where the Consensus Project was carried out. The relative risk of participation among vaccinated (≥2 doses) and unvaccinated women was estimated. Odds ratios (OR) of participation by vaccination status were estimated by logistic regression, adjusted by birthplace and birth cohort. RESULTS: Overall, 34,993 women were invited for screening: 13,006 (37.2%) participated and 10,062 of these agreed to participate in the Consensus intervention study. Among the invited women and screening participants, vaccinated women were 51.0% and 60.6%, respectively. Comparing vaccinated and unvaccinated women, the adjusted OR of screening participation was 1.80 (95% confidence interval (CI): 1.72-1.89), 2.17 (95% CI: 1.94-2.42), 1.59 (95% CI: 1.50-1.68) and 1.15 (95% CI: 0.86-1.54) for overall, Florence, Piedmont and Savona, respectively. About 33% of the invited women were unvaccinated and did not participate in screening: 25.8%, 59.5% and 64.2% of women born in Italy, in high migration pressure countries and in advanced development countries, respectively. CONCLUSIONS: Screening participation was higher among vaccinated than unvaccinated women. Active policies are needed to reduce inequalities, targeting the unscreened and unvaccinated population, particularly non-native women, to accelerate cervical cancer elimination in Italy.

EuroMed Cancer Network contributions to eliminating cervical cancer in low- and middle-income Mediterranean countries.

Background: Cervical cancer places a significant burden on low- and middle-income countries (LMICs). The EuroMed Cancer Network (EuMedCN) brings together cancer experts and stakeholders from the Mediterranean countries to promote sustainable cancer screening and support implementation of the WHO Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. Aim: To highlight the constructive role of EuMedCN in mitigating inequalities in access to cervical cancer prevention and screening across the Mediterranean LMICs. Methods: Through its workshops and meetings, EuMedCN members discussed new developments in cancer prevention and control, and how best to translate the WHO Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem into public health policies in the Mediterranean LMICs. This led to targeted actions in the selected countries. Results: Seven priority actions were implemented to improve cervical cancer screening in the Mediterranean LMICs. EuMedCN supported organized screening, new pilot technologies and enhancement of evaluation systems. Integrating cervical cancer screening into other disease programmes and fostering multidisciplinary networks were promoted as key to achieving targets of the WHO global strategy. Conclusion: International networks, such as EuMedCN, have the potential to bring together experts and stakeholders to share experiences and catalyse resource mobilization. They can support affordable and synergistic solutions for cervical cancer prevention.

Promoting healthy lifestyle habits among participants in cancer screening programs: Results of the randomized controlled Sti.Vi study.

Background: Unhealthy diets, physical inactivity, alcohol and tobacco consumption are among the leading risk factors for non-communicable diseases. It is estimated that around 40% of cancers could be prevented by adopting healthy lifestyles. Design and methods: The Stili di Vita (Sti.Vi) study was a randomized study for assessing the impact of healthy lifestyle interventions on anthropometric measures, metabolic parameters, and health outcomes among participants of cancer screening programs in Turin (Italy). Eligible women aged 50-54 years, invited to biennial mammography screening, and 58-years-old men and women, invited to a once-only sigmoidoscopy for colorectal cancer (CRC) screening were randomly allocated to Diet group (DG), Physical Activity group (PAG), Physical Activity plus Diet group (PADG), or control group (CG). Physical and eating habits, metabolic and anthropometric measurements, repeatedly collected, were the study outcomes. The active intervention, offered to participants assigned to the DG, PAG, and PADG arms, consisted of a basic module and an advanced module. The effect of the interventions was estimated through logistic regression or a difference in differences approach. A multiple imputation procedure was implemented to deal with missing values and q-values have been calculated in the presence of multiple hypothesis testing. Results: Out of the 8442 screened attendees, 1270 signed informed consent, while 1125 participants accomplished the baseline visit. Participants were equally distributed across the four treatments as following: 273 (24.3%) in DG, 288 (25.6%) in the PAG, 283 (25.1%) in PADG, and 281 (25%) in the CG. Participants assigned to DG or PADG increased their consumption of whole grains (OR = 1.77, 95% CI: 1.20-2.60 and OR = 1.55, 95% CI: 1.06-2.27, respectively) and legumes (OR = 1.77, 95% CI: 1.12-2.79 and OR = 2.24, 95% CI: 1.41-3.57, respectively), with respect to CG. The participants randomized to DG reduced processed meat and increased fruit consumption (OR = 2.57, 95% CI: 1.76-3.76 and OR = 2.38, 95% CI: 1.12-5.06, respectively). The effects were more evident in the CRC screening subgroup. No relevant difference was observed between PAG and CG. No impact was observed on physical activity habits. Conclusions: Our findings suggest that active interventions can increase awareness and induce diet changes. However, participation rate and compliance to the courses was quite low, innovative strategies to enhance participants' retention are needed, with the ultimate goal of increasing awareness and inducing positive lifestyle changes.

Transitional care: A new model of care from young age to adulthood.

INTRODUCTION: Transition of care represents the transfer from child to adult care. An effective transition maintains continuity of care and presents better clinical outcomes. This process has assumed growing relevance, thanks to improved survivorship of chronic paediatric patients. Actually, there is no a one-size model fitting for all transitions, but each Service organizes its own clinical pathway. AIM: The study proposes an organizational model for transition, differentiated according to patient complexity. METHODS: The working group discussed, through regular meetings, the appropriate transitional model for our Hospital. The working group defined a common scheme of transition and elaborated a synthetic document for patients. Then, the common model is adapted, through clinicians' contribution, for different diseases. The complexity assessment includes clinical data, nursing and social information. RESULTS: The working group defined a common model identifying the main information to be included and detailed in each transition report. The team defined two pathways based on patient's complexity. In case of good compensation and autonomous management, the adolescent is addressed towards standard transition process, a smoother transition from paediatric to adult care with direct connection among healthcare professionals. In case of complex clinical and/or social conditions, an Interdisciplinary Transition Group (ITG) is activated. The group preventively evaluates each patient in periodic meetings and provides a personalized planning of care. In order to define the complexity of a patient, clinical and social determinants are considered. Some diseases are considered complex by default, while others require ITG involvement in case of multiple comorbidities, severe clinical situation, concomitant social criticality and/or cognitive impairment. DISCUSSION: Transition of care represents an important phase in chronic diseases management. The proposed model assures a multidisciplinary approach, involving all specialists of both paediatric and adult teams. A key determinant of transition is information transmission. Then, the model proposes a common transition report format. Finally, a further perspective study is already in program, in order to assess clinical effectiveness.

[Did social isolation during the SARS-CoV-2 epidemic have an impact on the lifestyles of citizens?]

OBJECTIVES: to study the impact of social isolation, related to the SARS-CoV-2 epidemic, on lifestyles in Italy, with particular reference to physical activity, alcohol consumption, smoking, and eating habits. Moreover, to investigate the association between lifestyle changes during the pandemic and sociodemographic characteristics. DESIGN: epidemiological investigation based on a cross-sectional study. SETTING AND PARTICIPANTS: between April 21st and June 7th 2020, an electronic questionnaire to collect information on physical activity, alcohol consumption, smoking, and eating habits during the period of home containment was made available on the web. Respondents were recruited through non-probabilistic snowball sampling. The link to the electronic questionnaire was disseminated through institutional websites, social networks (Facebook, Twitter), and messaging systems such as WhatsApp, Telegram, and SMS. A total of 10,758 interviews were collected, of which 7,847 (73%) were complete for a minimum set of indicators (age, gender, and area of residence). MAIN OUTCOME MEASURES: reduction of physical activity, increase in alcohol consumption, increase in cigarette smoking, increase in consumption of unhealthy foods (processed meat, red meat or desserts) without increasing healthy foods (vegetables, legumes or whole grains) and, vice versa, increase in consumption of healthy foods without increasing unhealthy foods. RESULTS: the population under study consists of 7,847 people with a mean age of 48.6 years (standard deviation: 13.9). Most of respondents are women (71.3%), 92.5% have a high school or university degree and 91% live in Northern Italy. During home containment, 56% of interviewees reported they had reduced the time devoted to physical activity. In particular, this happened among older people and those living in large cities. More than 17% of respondents increased their alcohol consumption, especially men, those highly educated and those living in large urban centres. Older age and residence in the Southern Italy represent, instead, protective factors for this outcome. Among smokers, 30% increased cigarette consumption during the period of home containment, on average of 5.6 cigarettes per day. A small proportion of former smokers (0.6%) resumed smoking. With regard to eating habits, 3 out of 10 respondents (29.9%) reported an inappropriate eating behaviour (increasing unhealthy food without increasing healthy ones). This behaviour was less frequent among men (adjusted Prevalence Ratio 0.80, p=0.005). A lower percentage of respondents (24.5%) increased the consumption of healthy foods without increasing the consumption of unhealthy ones. CONCLUSIONS: the results of this survey show that social isolation during the SARS-CoV-2 pandemic has had an impact on citizens' behaviours. In particular, it was found a noteworthy increase in sedentariness, alcohol consumption, and tobacco smoking. A meaningful proportion of respondents reported a worsening of eating habits, especially among women. However, for each of the behavioural risk factors investigated, small proportions of respondents with resilient attitudes were also found, namely, capable of taking advantage of social isolation for improving their daily habits. Studying changes in lifestyles during a pandemic, identifying population groups most at risk of adopting unfavourable behaviours, is a useful tool for policy makers to plan targeted and effective public health interventions.

[Qualitative experiential analysis of the BRASS scale.] / Analisi qualitativa esperienziale di revisione della scala BRASS.

BACKGROUND: Hospital discharge can potentially represent an issue. Therefore, it is important to early identify patients at higher risk. A valid tool in this field is the Blaylock Risk Assessment Screening Score (BRASS). AIMS: The study aims to elaborate a simplified score system, throughout the contribution of healthcare professionals considering the single items of the original score. METHODS: The study included a qualitative analysis, conducted in order to draft the synthetic tool. Alongside, a statistical analysis was carried out. The findings of these two works were compared and joined in the realization of the proposed evaluation tool. RESULTS: The synthetic tool, developed by the working team, is composed by 20 items. The qualitative analysis agrees with the statistical approach. Moreover, the qualitative analysis consented to redefine some items, especially considering social support, and to include some additional information e.g. clinical problems. LIMITATIONS: The analysis considered only General Medicine wards, all located in the same Hospital. Therefore, generalisation to other settings or patients should be further tested. CONCLUSIONS: The synthetic tool, realized during the study, aims to improve the individuation of at-risk inpatients. The agreement between statistical and qualitative analysis can be considered a point of strength of our work. Our analysis consented to include some new items, improving overall organization. In conclusion, the working group aims to conduct further study in order to individuate the more appropriate cut-off of the new scoring method.

Cost-effectiveness of HIV screening in high-income countries: A systematic review.

INTRODUCTION: Over 2 million people in high-income countries live with HIV. Early diagnosis and treatment present benefits for infected subjects and reduce secondary transmissions. Cost-effectiveness analyses are important to effectively inform policy makers and consequently implement the most cost-effective programmes. Therefore, we conducted a systematic review regarding the cost-effectiveness of HIV screening in high-income countries. METHODS: We followed PRISMA statements and included all papers evaluating the cost-effectiveness of HIV screening in the general population or in specific subgroups. RESULTS: Thirteen studies considered routine HIV testing in the general population. The most cost-effective option appeared to be associating one-time testing of the general population with annual screening of high-risk groups, such as injecting-drug users. Thirteen studies assessed the cost-effectiveness of HIV screening in specific settings, outlining the attractiveness of similar programmes in emergency departments, primary care, sexually transmitted disease clinics and substance abuse treatment programmes. DISCUSSION: Evidence regarding the health benefits and cost-effectiveness of HIV screening is growing, even in low-prevalence countries. One-time screenings offered to the adult population appear to be a valuable choice, associated with repeated testing in high-risk populations. The evidence regarding the benefits of using a rapid test, even in terms of cost-effectiveness, is growing. Finally, HIV screening seems useful in specific settings, such as emergency departments and STD clinics.

The impact of intergenerational programs on children and older adults: a review.

ABSTRACTBackground:Elderly are at particular risk of social isolation. This condition significantly affects health; on the contrary, social involvement can be extremely advantageous. In this context, intergenerational programs improve interactions between different ages. Then, we conducted a review regarding intergenerational programs, to summarize the effects of these activities on both elderly and children. METHODS: Our review followed the PRISMA statements. We considered papers reporting data about intergenerational programs involving children (preschool and elementary) and elderly. RESULTS: The final selection obtained 27 sources. Ten studies evaluated children's outcomes outlining the positive impact of intergenerational programs upon children's perception of elderly. The effects on older participants were variegated considering well-being, depression, self-reported health, and self-esteem. Moreover, the retrieved studies outlined the importance of a careful organization and of a specific training for all staff members. The staff involved in similar programs appeared, overall, highly satisfied. DISCUSSION: The positive impact on children of intergenerational programs is proved at both short- and long-term. Moreover, despite the different outcomes considered and the variable results, these programs resulted overall beneficial on elderly participants. Finally, similar activities resulted feasible even in case of older adults with dementia.

HIV screening in pregnant women: A systematic review of cost-effectiveness studies.

INTRODUCTION: Vertical transmission represents the major route of HIV infection for children. However, the preventive interventions available are extremely effective. This review summarizes evidence regarding the cost-effectiveness of mother-to-child-transmission preventive screenings, to help policy makers in choosing the optimal antenatal screening strategy. METHODS: A systematic review following PRISMA guidelines was conducted, using 3 databases: PubMed, Scopus, and Cost-Effectiveness Analysis Registry. All articles regarding HIV screening to avoid vertical transmission were included. RESULTS: The review included 21 papers. Seven studies assessed the cost-effectiveness of universal antenatal screening during early gestation. Two papers considered the integration of HIV screening with other medical interventions. Eight works estimated the cost-effectiveness of HIV screening in late pregnancy. Finally, 4 papers considered the combination of multiple strategies. The selected papers focused on both developed and developing countries, with a different HIV prevalence. The characteristics and methodology of the studies were heterogeneous. However, all studies agreed about the main findings, outlining the cost-effectiveness of both universal antenatal screening and HIV rescreening in late pregnancy. Cost-effectiveness improved when HIV burden increased. The major findings were proved to be robust across various scenarios when tested in sensitivity analysis. CONCLUSIONS: The review confirmed the cost-effectiveness not only of HIV universal antenatal screening but also of rescreening in late gestation in both developed and developing countries. Universal screening is cost-effective even in case of extremely low HIV prevalence. Therefore, to maximize screening, coverage appears as a worldwide priority. In certain settings, a targeted screening towards high-risk groups could be a valuable option.

Analysis of users and reasons for use of a physician-on-call service in an Italian local health unit.

BACKGROUND: In recent years, several countries have proposed changes to primary care organisation. OBJECTIVE: Our study investigated the characteristics of 'physician-on-call' usage in a local health unit of Lombardy (ASL MI1). METHODS: We analysed the incoming calls to the Operative Medical Central Station and collected the user characteristics, the call reasons and the outcomes from 1 October to 31 December 2012. Then, we randomly extracted 10% of the call sample from this period. We focused on two outputs: telephone advice (TA) and emergency department referral. We fit a logistic regression model to identify potential predictors of these outputs. RESULTS: In total, we evaluated 2146 calls. Women made most of the calls. Older age was associated with the referral to emergency care [adjusted odds ratio (aOR) 3.1], while paediatric calls were associated with TA (aOR 1.9). Information requests were related to TA (aOR 2.3), while cardiovascular symptoms (aOR 3.5), pain (aOR 2.6) and traumas (aOR 4.7) were linked to emergency care. CONCLUSIONS: Our study outlined the increasing use of TA, particularly for calls regarding paediatric patients. In contrast, calls for elderly patients were more frequently referred to emergency care. These findings led to the implementation of an age-targeted educational programme. Overall, our observations highlighted that women used the physician-on-call service more frequently than men. Furthermore, some reasons for calling were significantly associated with emergency care.

Risks and Threats of Social Media Websites: Twitter and the Proana Movement.

In recent years, there was a spread of "proanorexia" Web sites. The aim of our study is to investigate the presence, popularity, and content of the "proana" accounts on Twitter. On January 2015, we used "Twitter Search" to retrieve the "proana" accounts. For each account, we analyzed the number of followers, tweets, and the biographical information of the users. We followed these accounts for 4 weeks, assessing the variations in followers and tweets. We also investigated the most used hashtags and the main contents of these profiles. We retrieved 341 accounts. These accounts were popular (mean followers: 2360.9, range: 5-32,700) and active (mean tweets: 4351.2, range: 5-85,700). The users were mostly girls (97.9 percent), in general teenagers (mean age: 17.9 years, range: 12-28). Only around six percent of the accounts presented a warning text about the dangerous content. Each week, we found a mean increase in both followers and tweets. The five most used hashtags resulted in descending order as follows: "thinspo," "thinspiration," "Thin15," "EDprobs," and "proana." The most commonly used contents were in the following order: autobiographic, "thinspiration" photos (inspirational photos of extremely thin girls), "thinspiration" quotes (motivational mottos), "ana tips" (advices for weight loss), and "fasting competition." We underlined a concerning high number and popularity of Twitter proanorexia groups. These accounts contain dangerous information, especially considering the young age of the users. Given the lack of warnings in almost all the accounts, a first step to control this phenomenon could be the increase of such written alerts.

Animal assisted intervention: A systematic review of benefits and risks.

INTRODUCTION: The therapeutic use of animals has been debated for decades, and its use explored in a variety of settings and populations. However, there is no uniformity on naming these interventions. Evidence based knowledge is essential to implement effective strategies in hospital. This review focused on the use of animal programs for hospitalized patients, and considered the potential risks. METHODS: The following databases were searched: PubMed, Scopus, PsychInfo, Ebsco Animals, PROQUEST, Web of Science, CINAHL, and MEDLINE, and PRISMA guidelines were adhered to. RESULTS: Out of 432 articles were identified 36 articles suitable for inclusion into the review. Data was heterogeneous in terms of age of patient, health issue, animals used and the length of interactions, which made comparison problematic. Studies on children, psychiatric and elderly patients were the most common. The animal-intervention programs suggested various benefits such as reducing stress, pain and anxiety. Other outcomes considered were changes in vital signs, and nutritional intake. Most studies used dogs, but other animals were effectively employed. The major risks outlined were allergies, infections and animal-related accidents. Zoonosis was a possible risk, as well as common infections as Methicillin-resistant Staphylococcus Aureus. The implementation of simple hygiene protocols was effective at minimizing risk. The literature suggested that the benefits outweighed by far the risks. CONCLUSION: The human relationship with animals can be useful and relatively safe for inpatients with various problems. Moreover, the implementation of security precautions and the careful selection of patients should minimize the risks, particularly those infection-related. Many aspects remain unclear, further studies are required.

Human mesenchymal stem cells modulate cellular immune response to islet antigen glutamic acid decarboxylase in type 1 diabetes.

CONTEXT: Mesenchymal stem cells (MSCs) exert an immunosuppressive effect on the immune system. However, studies on the immunomodulatory potential of MSCs in type 1 diabetes are lacking. OBJECTIVE: We aimed to evaluate whether human MSCs may inhibit in vitro pancreatic islet antigen-specific T cell activation in type 1 diabetes. DESIGN: Human MSCs were isolated and characterized. Peripheral blood mononuclear cells (PBMCs) were obtained from nine type 1 diabetic patients at disease onset and 13 healthy control subjects. IFN-gamma, IL-10, and IL-4 enzyme-linked immunospot responses of lymphocytes incubated with glutamic acid decarboxylase 65 (GAD65) were investigated in PBMC cultures and PBMC/MSC cocultures. Levels of prostaglandin E2 (PGE2), IFN-gamma, IL-4, and IL-10 in supernatants were measured by ELISA. PGE2 inhibition experiments with NS-398 and indomethacin were also performed. RESULTS: Five diabetic patients were identified with a positive PBMC IFN-gamma response to GAD65 and negative IL-10 and IL-4 response. PBMC/MSC cocultures resulted in a significant decrease in the number of spots and in detection of IL-4-secreting cells. PGE2 inhibitors abrogated the immune-suppressive effect, indicating an involvement of PGE2 production, and the constitutive production of PGE2 by MSCs was enhanced in PBMC/MSC coculture. Moreover, in GAD-responder patients, GAD-stimulated PBMC/MSC cocultures significantly decreased secretion of IFN-gamma and IL-10 and increased secretion of IL-4. CONCLUSIONS: These results provide evidence that human MSCs abrogate in vitro a proinflammatory T helper type 1 response to an islet antigenic stimulus in type 1 diabetes. MSCs induce IL-4-producing cells, suggesting a possible switch to an antiinflammatory T helper type 2 signaling of T cells.