Iron capture through CD71 drives perinatal and tumor-associated Treg expansion

: Beside suppressing immune responses, regulatory T cells (Tregs) maintain tissue homeostasis and control systemic metabolism. Whether iron is involved in Treg-mediated tolerance is completely unknown. Here, we showed that the transferrin receptor CD71 was upregulated on activated Tregs infiltrating human liver cancer. Mice with a Treg-restricted CD71 deficiency spontaneously developed a scurfy-like disease, caused by impaired perinatal Treg expansion. CD71-null Tregs displayed decreased proliferation and tissue-Treg signature loss. In perinatal life, CD71 deficiency in Tregs triggered hepatic iron overload response, characterized by increased hepcidin transcription and iron accumulation in macrophages. Lower bacterial diversity, and reduction of beneficial species, were detected in the fecal microbiota of CD71 conditional knock-out neonates. Our findings indicate that CD71-mediated iron absorption is required for Treg perinatal expansion and related to systemic iron homeostasis and bacterial gut colonization. Therefore, we hypothesize that Tregs establish nutritional tolerance through competition for iron during bacterial colonization after birth

The United Nations Office on Drugs and Crime's efforts to strengthen a culture of prevention in low- and middle-income countries.

This article discusses how decision-makers can be supported to strengthen a culture of prevention. This article presents an example of the United Nations Office on Drugs and Crime's (UNODC) work to engage with decision-makers to create readiness, demand, and capacity for evidence-based prevention programming among them, particularly in low- and middle-income countries. First, we utilized two of the UNODC's data sources to describe the context where the UNODC's prevention efforts take place. Analysis of the first dataset on prevention activities implemented globally revealed a gap in translating evidence into practice on a global scale. The second dataset consisted of UNODC policy documents mandating and guiding global action to address substance use. The analysis showed that at the level of political frameworks, prevention is gradually gaining more attention but is still frequently left in the shadow of health- and law enforcement-related issues. In addition, these guiding documents did not reflect fully the current scientific understanding of what constitutes an effective prevention response. Against this background, the feasibility of the UNODC's efforts to bridge the science-practice gap in the field of prevention was discussed by presenting the results from the UNODC's regional capacity-building seminars focused on the role of monitoring and evaluation in prevention programming. The results showed potential of this capacity building to affect the attitudes and knowledge of targeted decision-makers. Such efforts to increase decision-makers' readiness and ultimately their endorsement, adoption, and ongoing support of evidence-based preventive interventions should be continued and intensified

Priorities for addressing substance use disorder in humanitarian settings

BACKGROUND: Populations affected by humanitarian emergencies are vulnerable to substance (alcohol and other drug) use disorders, yet treatment and prevention services are scarce. Delivering substance use disorder treatment services in humanitarian settings is hampered by limited guidance around the preparation, implementation, and evaluation of substance use disorder treatment programs. This study aims to identify and prioritize key gaps and opportunities for addressing substance use disorder in humanitarian settings. METHODS: UNODC convened a consultation meeting (n = 110) in coordination with UNHCR and WHO and administered an online survey (n = 34) to, thirteen program administrators and policymakers, eleven service providers, nine researchers, and one person with lived experience to explore best practices and challenges to addressing substance use disorder in diverse populations and contexts. Participants presented best practices for addressing substance use disorder, identified and ranked challenges and opportunities for improving the delivery of substance use disorder treatment interventions, and provided recommendations for guidelines that would facilitate the delivery of substance use disorder treatment services in humanitarian emergencies. RESULTS: Participants agreed on key principles for delivering substance use disorder treatment in humanitarian settings that centered on community engagement and building trust, integrated service delivery models, reducing stigma, considering culture and context in service delivery, and an ethical ‘do no harm’ approach. Specific gaps in knowledge that precluded the delivery of appropriate substance use disorder treatment include limited knowledge of the burden and patterns of substance use in humanitarian settings, the effectiveness of substance use disorder treatment services in humanitarian settings, and strategies for adapting and implementing interventions for a given population and humanitarian context. Participants emphasized the need to strengthen awareness and commitment related to the burden of substance use disorder treatment interventions among communities, practitioners, and policymakers in humanitarian settings. CONCLUSIONS: Results from this consultation process highlight existing gaps in knowledge related to the epidemiology and treatment of substance use disorders in humanitarian emergencies. Epidemiological, intervention, and implementation research as well as operational guidance are needed to fill these gaps and improve access to substance use treatment services in humanitarian settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13031-021-00407-z

Comparison of Mobile Phone Ownership of Participants from Tanga and Muheza.

Comparison of Mobile Phone Ownership of Participants from Tanga and Muheza.</p

Mobile Phone Possession and Usage Patterns of the Study Participants.

Mobile Phone Possession and Usage Patterns of the Study Participants.</p

Comparison of Readiness to Use Mobile Phone for Learning about Substances of Participants from Tanga City and Muheza.

Comparison of Readiness to Use Mobile Phone for Learning about Substances of Participants from Tanga City and Muheza.</p

Socio-demographic characteristics of the study participants N (%).

Socio-demographic characteristics of the study participants N (%).</p

Prolonged 14-day continuous infusion of high-dose ifosfamide for patients with relapsed and refractory high-grade osteosarcoma: a retrospective multicentre cohort study

Abstract Background The prognosis of patients with Relapsed/Refractory Osteosarcoma (R/R OS) remains dismal without an agreement on systemic therapy. The use of High-Dose Ifosfamide (14 g/sqm) with an external pump in outpatient setting (14-IFO) in R/R OS patients is limited. This study represents the first retrospective cohort analysis focused on evaluating the activity and toxicity of 14-IFO in this setting. Patients and methods The study investigated 14-IFO activity, in terms of tumour response according to RECIST 1.1 criteria, as well as survival rates and toxicity, according to CTCAE v.5. Results The trial enrolled 26 patients with R/R OS. The Overall Response Rate (ORR) and Disease Control Rate (DCR) obtained was 23% and 57.5%, respectively. Patients with relapsed OS showed a higher ORR (45%) and DCR (82%) compared to refractory patients, irrespective of the number of prior treatment lines received. The achievement of disease control with 14-IFO administration enabled 27% of patients to undergo new local treatment. Four-month Progression-Free Survival (PFS) was 54% for all patients and 82% for the relapsed OS sub-group. Median Overall Survival (OSurv) was 13.7 months, with 1-year OSurv of 51% for all patients and 71% for relapsed patients. Age over 18 years and the presence of refractory disease were identified as negative prognostic factors for this patient cohort. A total of 101 cycles were evaluated for toxic assessment, demonstrating a tolerable profile without grade 3–4 non-haematological toxicities. Conclusions 14-IFO should be considered a viable treatment option for R/R OS, particularly due to its well tolerated toxicity profile and the potential for home-administration, which can improve patient quality of life without compromising efficacy