Glioblastomas exploit truncated O - linked glycans for local and distant immune modulation via the macrophage galactose-type lectin

Glioblastoma is the most aggressive brain malignancy, for which immunotherapy has failed to prolong survival. Glioblastoma-associated immune infiltrates are dominated by tumor-associated macrophages and microglia (TAMs), which are key mediators of immune suppression and resistance to immunotherapy. We and others demonstrated aberrant expression of glycans in different cancer types. These tumor-associated glycans trigger inhibitory signaling in TAMs through glycan-binding receptors. We investigated the glioblastoma glycocalyx as a tumor-intrinsic immune suppressor. We detected increased expression of both tumor-associated truncated O-linked glycans and their receptor, macrophage galactose-type lectin (MGL), on CD163+ TAMs in glioblastoma patient-derived tumor tissues. In an immunocompetent orthotopic glioma mouse model overexpressing truncated O-linked glycans (MGL ligands), high-dimensional mass cytometry revealed a wide heterogeneity of infiltrating myeloid cells with increased infiltration of PD-L1+ TAMs as well as distant alterations in the bone marrow (BM). Our results demonstrate that glioblastomas exploit cell surface O-linked glycans for local and distant immune modulation.</p

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Development and evaluation of diversity-oriented competence training for the treatment of depressive disorders

Studies in Europe indicate that some ethnic minorities have higher rates of mental disorders and less favorable treatment outcomes than their counterparts from majority groups. To date, efforts regarding training to reduce disparities have mainly focused on ethnocultural competences of therapists, with less attention paid to other aspects of diversity, such as sex/gender and socioeconomic status. In this study, we aim to determine the effectiveness of a population-specific, diversity-oriented competence training designed to increase therapists’ competencies to integrate aspects of diversity features in clinical assessment, diagnosis, and treatment of depressive disorders in Turkish- and Moroccan-Dutch patients. A group of 40 therapists were location-based assigned to either training or a control condition (no training). Self-reported diversity competence, a knowledge test, and therapists’ satisfaction with training were used to monitor the training and to measure competence levels at baseline, post-training, and three-month follow-up. Attitude-awareness and knowledge components of the self-reported diversity competence and test-measured knowledge increased in the training condition. Most gains remained stable at follow-up except test-measured knowledge after controlling for percentage of ethnic minority patients in caseload. There were no changes regarding therapists’ self-reported skills. Therapists expressed medium–high satisfaction with the training, acknowledging the relevance of diversity competence for their daily practice. Future training must ensure better adjustment to therapists’ pre-existing knowledge and be followed by long-term efforts to maintain competence levels and enhance competence transfer within teams

Schema therapy for borderline personality disorder:A comprehensive review of its empirical foundations, effectiveness and implementation possibilities

Borderline personality disorder is a serious psychiatric disorder for which the effectiveness of the current pharmacotherapeutical and psychotherapeutic approaches has shown to be limited. In the last decades, schema therapy has increased in popularity as a treatment of borderline personality disorder; however, systematic evaluation of both effectiveness and empirical evidence for the theoretical background of the therapy is limited. This literature review comprehensively evaluates the current empirical status of schema therapy for borderline personality disorder. We first described the theoretical framework and reviewed its empirical foundations. Next, we examined the evidence regarding effectiveness and implementability. We found evidence for a considerable number of elements of Young's schema model; however, the strength of the results varies and there are also mixed results and some empirical blanks in the theory. The number of studies on effectiveness is small, but reviewed findings suggest that schema therapy is a promising treatment. In Western-European societies, the therapy could be readily implemented as a cost-effective strategy with positive economic consequences. Highlights ► Offers both theoretical description and empirical review of the schema model for BPD. ► Evidence exists for a number of schema constructs and mechanisms. ► The extant efficacy studies show positive outcomes of schema therapy for BPD. ► Schema therapy seems a societal cost-effective approach. ► Further work is required to achieve full empirical support of the model and therapy. Keywords: Borderline personality disorder, Schema therapy, Young's schema model, Early maladaptive schema, Schema mode, Effectivenes