There are numerous definitions of polypharmacy to describe the use of many medications among older adults, but there is a need to clarify if they are purposive and meaningful. By means of a systematic review, we identified definitions of polypharmacy used in multimorbid older adults (≥65 years). We evaluated if the definitions align among the domains of research, clinical practice, and public health and appraised whether concepts of polypharmacy are based on strong foundations. More than 46 definitions of polypharmacy were retrieved from 348 publications (research: n = 243; clinical practice: n = 88; public health: n = 17). Several thresholds based on the number of medications were mentioned. The majority of the publications (n = 202, 58%) used a minimal threshold of five medications. Heterogeneous qualitative definitions were identified, mostly stating that polypharmacy is “more drugs than needed”. There was no significant divergence between domains as to the type of definitions used, although qualitative definitions were more common in clinical practice. Nearly half (n = 156, 47%) of the publications provided no justification for the polypharmacy definition used. The wide variety of definitions for polypharmacy precludes comparisons, appropriate identification and management of polypharmacy in multimorbid older adults. Standardized definitions would allow more coherent judgments regarding the individual and collective stakes of polypharmacy.

Immunotherapy of tumors and of melanoma in particular has a long history, and recently this therapeutic approach found a reliable scientific rationale. This biological therapy aims to teach the patient's immune system to recognize the antigens expressed on tumor cells and destroy them, leaving normal cells intact. The success of this therapy highly depends on the selection of target antigens that are essential for tumors growth and progression. The overexpression of GM(3) ganglioside 1 and especially the expression of its metabolite GM(3) lactone 2 characterize murine and human melanomas, playing an important role in tumor progression and making such self-antigens potential targets for the immunotherapy of these neoplasms. Although more immunogenic than its precursor, GM(3) lactone 2 is unsuitable to be used in immunotherapy as a melanoma-associated antigen (MAA) because it is unstable under physiological conditions. We designed and synthesized the hydrolytically stable mimetic 3, which is remarkably simpler than the native lactone 2; after conjugation of 3 to the protein carrier keyhole-limpet hemocyanin (KLH), the obtained glycoprotein 5 was used as the immunogen in vivo to successfully elicit specific antimelanoma antibodies. In fact, no appreciable binding to GM(1) was observed. Capitalizing on the stability and on the reduced structural complexity of mimetic 3, the immunostimulant 5 we report represents a new promising synthetic glycoconjugate for the immunotherapy of melanoma.

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Patient-oriented research (POR) has received increasing attention in recent years. In this approach, patients' experiential knowledge, derived from their experiences of living with a condition or illness and of interacting with the healthcare system, is recognized, valued, and seen as complementary to scientific knowledge. Early career researchers (ECRs) are the next generation of researchers, but little is known about how they perceive POR. In this study, ECRs were invited to reflect on what POR is, how patients can best contribute to research, and ECRs' own role in developing POR. Using a technique designed to collect expert opinions and find consensus-the Delphi method-a panel of 16 ECRs responded, in three rounds, to three questionnaires, with the second and third being built on responses to the preceding ones. Based on their understanding, the panelists agreed that the most important element in defining POR would be valuing, mobilizing, and legitimizing the experiential knowledge of patients who live with a particular health condition. Panelists considered patients to be integral members of the research team, but were less convinced that they should be considered co-researchers. The panelists saw themselves as taking part in developing POR by sharing information, teaching, and encouraging POR among their peers, as well as by participating actively in organizations interested in POR. This is the first study to examine the perspectives of ECRs, who, along with many others, have an important role in supporting the ongoing development of POR so that it becomes more widely adopted.

Conformation analysis and synthesis of 2, a hydrolytically stable mimetic of the tumour antigen, GM3 lactone ganglioside (1 a), is reported (see figure for superimposed images of 1 a and 2). The interaction between 2 and wheat germ agglutinin lectin showed that 2 is a veritable mimetic of a sialyl‐containing saccharide. DOPC/DOPE liposomes containing thioether 3 were also prepared and characterized; these could prove to be promising carriers for the production of monoclonal antibodies.

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Aims Depression in type 2 diabetes may heavily affect the course of the disease. In this study, we investigated, among new cases with type 2 diabetes, the incidence and clinical predictors of depression and determined the extent to which depression constitutes a risk factor for acute and long-term diabetes complications and mortality. Methods In this population-based retrospective cohort study, incident cases of type 2 diabetes without a prior history of depression were identified from the administrative databases of the Emilia-Romagna Region, Italy, between 2008 and 2017 and followed up until 2020. Logistic regression models were used to identify the predictors of depression. Cox regression models were used to estimate the risk of acute complications over three years, and the risk of long-term complications and mortality over ten years. Results Incident cases with type 2 diabetes were 30,815, of whom 5146 (16.7%) developed depression. The predictors of depression onset were as follows: female sex, age > 65 years, living in rural areas and comorbid diseases. Depression in type 2 diabetes was associated with a 2.3-fold risk of developing acute complications, 1.6-fold risk of developing long-term complications and 2.8-fold mortality risk. Conclusions Our findings highlight that depression is associated with an increased risk for complications in type 2 diabetes and mortality and should not be neglected. Therefore, it is important to promote screening activities and introduce targeted and personalized treatment for depression in order to reduce the risk of poor short- and long-term outcomes of diabetes.