miRNAs as predictive biomarkers of response to treatment in pediatric patients with acute lymphoblastic leukemia.

MicroRNAs (miRNAs/miRs) are promising prognostic biomarkers in pediatric acute lymphoblastic leukemia (ALL). The present study aimed to identify miRNAs that could serve as prognostic biomarkers or as novel therapeutic targets in ALL. The expression levels of 84 miRNAs were assessed in the bone marrow aspirates of 10 pediatric patients with newly diagnosed ALL at diagnosis and on day 33 of induction of the ALL Intercontinental Berlin-Frankfurt-Münster 2009 protocol, and associations with established prognostic factors were evaluated. The levels at diagnosis of 25 miRNAs were associated with ≥2 prognostic factors. Higher expression levels of let-7c-5p, miR-106b-5p, miR-26a-5p, miR-155-5p, miR-191-5p, miR-30b-5p and miR-31-5p were significantly associated with a good prednisone response. The expression levels of miR-125b-5p, miR-150-5p and miR-99a-5p were significantly higher in standard- or intermediate-risk patients compared with those in high-risk patients (P=0.017, P=0.033 and P=0.017, respectively), as well as in those with a complete response at the end of induction (P=0.044 for all three miRNAs). The change in expression levels between diagnosis and the end of induction differed significantly between risk groups for three miRNAs: miR-206, miR-210 and miR-99a (P=0.033, P=0.047 and P=0.008, respectively), with the post induction levels of miR-206 increased in high-risk patients, whilst miR-210 and miR-99a levels were increased in intermediate/standard risk patients. Therefore, miRNAs that could be integrated into the risk stratification of pediatric ALL after further evaluation in larger patient cohorts were identified.

Inhibition of the Renin-Angiotensin System Reduces Gene Expression of Inflammatory Mediators in Adipose Tissue Independent of Energy Balance.

Obesity is a growing health problem worldwide. The renin-angiotensin system (RAS) is present in adipose tissue, and evidence suggests that it is involved in both diet-induced obesity and the inflammation associated with obesity. The present experiments determined the effect of (1) different angiotensin-converting enzyme (ACE) inhibitors (captopril, perindopril, enalapril) and angiotensin receptor blockers (ARBs: telmisartan, losartan) on adiposity of mice fed a high-fat diet for 28 days (2); acute treatment with the ACE-inhibitor captopril on gene expression of inflammatory markers in mice fed a high-fat diet (HFD); and (3) short-term (2 days) and chronic (28 days) treatment of ACE-inhibition on energy expenditure (EE) and energy balance in mice fed HFD ad libitum (AL), as well as receiving HFD limited to the amount of calories eaten by controls (pair-fed (PF) group). Body weight, food intake, adiposity and plasma leptin were lower in ACE inhibitor or ARB-treated groups over 28 days compared with HFD untreated mice. Short-term treatment with captopril led to increased EE relative to the level in the PF group. After 28 days, EE was lower in both captopril-treated and PF mice compared with AL, but the effect was greater in the captopril-treated group. Adiponectin was elevated in captopril-treated mice, but not in PF mice, after both 2 and 28 days. Additionally, acute RAS blockade in HFD-fed mice reduced mRNA expression for MCP-1, IL-6, TLR4, and leptin in adipose tissue relative to values in untreated groups. These data demonstrate that ACE inhibition and angiotensin receptor blockade reduce food intake to produce weight loss and suggest that the anti-inflammatory effects of ACE inhibition may be independent of weight loss.

Diagnostic Capacity for Invasive Fungal Infections in the Greek Paediatric Haematology-Oncology Units: Report from the Infection Working Group of the Hellenic Society of Paediatric Haematology-Oncology.

An audit based on a specific questionnaire was attempted, in order to investigate the mycology laboratory diagnostic capacity for invasive fungal diseases (IFDs) in Greek Paediatric Haematology-Oncology departments/units. The study provided the relevant information for the years 2019 and 2020 and included data from all units, concerning culture-based methods and direct microscopy, phenotypic and molecular identification, sensitivity testing, serology and molecular diagnosis, as well as therapeutic drug monitoring. The target was mostly to reveal the level of laboratory coverage for hospitalised paediatric patients, independently of the possibility of performing the tests in the host hospital, or otherwise to refer the specimens elsewhere. In total, the current study demonstrated that the most important facilities and services regarding the IFD diagnostics for paediatric haematology-oncology patients in Greece are available and relatively easily accessible, with a reasonable turnaround time. Acting as an initial registry for further improvements, the audit can serve as a valuable approach to the actual situation and future perspectives. A national clinical mycology network under the auspices of the relevant scientific societies will probably facilitate collaboration between all the departments (clinical and laboratory) involved in invasive fungal infections and provide an easier approach to any necessary test for any hospitalised patient.

Perspectives of patients, carers and mental health staff on early warning signs of relapse in psychosis: a qualitative investigation.

BACKGROUND: Relapse prevention strategies based on monitoring of early warning signs (EWS) are advocated for the management of psychosis. However, there has been a lack of research exploring how staff, carers and patients make sense of the utility of EWS, or how these are implemented in context. AIMS: To develop a multiperspective theory of how EWS are understood and used, which is grounded in the experiences of mental health staff, carers and patients. METHOD: Twenty-five focus groups were held across Glasgow and Melbourne (EMPOWER Trial, ISRCTN: 99559262). Participants comprised 88 mental health staff, 21 patients and 40 carers from UK and Australia (total n = 149). Data were analysed using constructivist grounded theory. RESULTS: All participants appeared to recognise EWS and acknowledged the importance of responding to EWS to support relapse prevention. However, recognition of and acting on EWS were constructed in a context of uncertainty, which appeared linked to risk appraisals that were dependent on distinct stakeholder roles and experiences. Within current relapse management, a process of weighted decision-making (where one factor was seen as more important than others) described how stakeholders weighed up the risks and consequences of relapse alongside the risks and consequences of intervention and help-seeking. CONCLUSIONS: Mental health staff, carers and patients speak about using EWS within a weighted decision-making process, which is acted out in the context of relationships that exist in current relapse management, rather than an objective response to specific signs and symptoms.

Developing a Hypothetical Implementation Framework of Expectations for Monitoring Early Signs of Psychosis Relapse Using a Mobile App: Qualitative Study.

BACKGROUND: Relapse is a common experience for people diagnosed with psychosis, which is associated with increased service costs and profound personal and familial distress. EMPOWER (Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery) is a peer worker-supported digital intervention that aims to enable service users to self-monitor their mental health with the aim of encouraging self-management and the shared use of personal data to promote relapse prevention. Digital interventions have not been widely used in relapse prevention and, therefore, little is currently known about their likely implementation-both within trials and beyond. OBJECTIVE: Seeking the perspectives of all relevant stakeholder groups is recommended in developing theories about implementation because this can reveal important group differences in understandings and assumptions about whether and for whom the intervention is expected to work. However, the majority of intervention implementation research has been retrospective. This study aimed to discover and theoretically frame implementation expectations in advance of testing and synthesize these data into a framework. METHODS: To develop a hypothetical implementation framework, 149 mental health professionals, carers, and people diagnosed with psychosis participated in 25 focus groups in both Australia and the United Kingdom. An interview schedule informed by the normalization process theory was used to explore stakeholders' expectations about the implementation of the EMPOWER intervention. Data were analyzed using thematic analysis and then theoretically framed using the Medical Research Council guidelines for understanding the implementation of complex interventions. RESULTS: All groups expected that EMPOWER could be successfully implemented if the intervention generated data that were meaningful to mental health staff, carers, and service users within their unique roles. However, there were key differences between staff, carers, and service users about what facilitators and barriers that stakeholders believe exist for intervention implementation in both the cluster randomized controlled trial stage and beyond. For example, service user expectations mostly clustered around subjective user experiences, whereas staff and carers spoke more about the impact upon staff interactions with service users. CONCLUSIONS: A hypothetical implementation framework synthesized from stakeholder implementation expectations provides an opportunity to compare actual implementation data gathered during an ongoing clinical trial, giving valuable insights into the accuracy of these stakeholders' previous expectations. This is among the first studies to assess and record implementation expectations for a newly developed digital intervention for psychosis in advance of testing in a clinical trial. TRIAL REGISTRATION: ISRCTN Registry ISRCTN99559262; http://www.isrctn.com/ISRCTN99559262.