Blockade of MIF-CD74 Signalling on Macrophages and Dendritic Cells Restores the Antitumour Immune Response Against Metastatic Melanoma

Mounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. While immunotherapies have shown a remarkable success in melanoma treatment, patients develop resistance by mechanisms that include the establishment of an immune suppressive tumor microenvironment. Thus, understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that macrophages (MOs) and dendritic cells (DCs) are suppressed in metastatic melanoma and that the Ig-CDR-based peptide C36L1 is able to restore MOs and DCs' antitumorigenic and immunogenic functions and to inhibit metastatic growth in lungs. Specifically, C36L1 treatment is able to repolarize M2-like immunosuppressive MOs into M1-like antitumorigenic MOs, and increase the number of immunogenic DCs, and activated cytotoxic T cells, while reducing the number of regulatory T cells and monocytic myeloid-derived suppressor cells in metastatic lungs. Mechanistically, we find that C36L1 directly binds to the MIF receptor CD74 which is expressed on MOs and DCs, disturbing CD74 structural dynamics and inhibiting MIF signaling on these cells. Interfering with MIF-CD74 signaling on MOs and DCs leads to a decrease in the expression of immunosuppressive factors from MOs and an increase in the capacity of DCs to activate cytotoxic T cells. Our findings suggest that interfering with MIF-CD74 immunosuppressive signaling in MOs and DCs, using peptide-based immunotherapy can restore the antitumor immune response in metastatic melanoma. Our study provides the rationale for further development of peptide-based therapies to restore the antitumor immune response in metastatic melanoma

How does gender influence the recognition of cardiovascular risk and adherence to self-care recommendations? : a study in polish primary care

Background: Studies have shown a correlation between gender and an ability to change lifestyle to reduce the risk of disease. However, the results of these studies are ambiguous, especially where a healthy lifestyle is concerned. Additionally, health behaviors are strongly modified by culture and the environment. Psychological factors also substantially affect engagement with disease-related lifestyle interventions. This study aimed to examine whether there are differences between men and women in the frequency of health care behavior for the purpose of reducing cardiovascular risk (CVR), as well as cognitive appraisal of this type of risk. We also aimed to identify the psychological predictors of engaging in recommended behavior for reducing the risk of cardiovascular disease after providing information about this risk in men and women. Methods: A total of 134 consecutive eligible patients in a family practice entered a longitudinal study. At initial consultation, the individual’s CVR and associated health burden was examined, and preventive measures were recommended by the physician. Self-care behavior, cognitive appraisal of risk, and coping styles were then assessed using psychological questionnaires. Six months after the initial data collection, the frequency of subjects’ self-care behavior was examined. Results: We found an increase in health care behavior after providing information regarding the rate of CVR in both sexes; this increase was greater for women than for men. Women followed self-care guidelines more often than men, particularly for preventive measures and dietary advice. Women were more inclined to recognize their CVR as a challenge. Coping style, cognitive appraisal, age, level of health behaviors at baseline and CVR values accounted for 48% of the variance in adherence to self-care guidelines in women and it was 52% in men. In women, total risk of CVD values were most important, while in men, cognitive appraisal of harm/loss was most important. Conclusions: Different predictors of acquisition of health behavior are encountered in men and women. Our results suggest that gender-adjusted motivation models influencing the recognition process need to be considered to optimize compliance in patients with CVR

Programa de intervención en representaciones de creatividad y motivación académica de adolescentes

Creativity and its promotion are widespread concerns in education. However, few efforts have been made to implement intervention programs designed to promote creativity and other related aspects (e.g., academic motivation). The Future Problem Solving Program International (FPSPI), aimed for training creativity representations and creative problem solving skills in young people, has been one of the most implemented programs. This intervention’s materials and activities were adapted for Portuguese students, and a longitudinal study was conducted. The program was implemented during four months, in weekly sessions, by thirteen teachers. Teachers received previous training for the program and during the program’s implementation. Intervention participants included 77 Basic and Secondary Education students, and control participants included 78 equivalent students. Pretest-posttest measures of academic motivation and creativity representations were collected. Results suggest a significant increase, in the intervention group, in motivation and the appropriate representations of creativity. Practical implications and future research perspectives are presented.A criatividade e sua promoção geram grande preocupação em educação. Contudo, poucos esforços têm existido para implementar programas destinados a sua promoção e de outros aspetos relacionados (e.g., motivação acadêmica). O Future Problem Solving Program International (FPSPI), criado para melhorar as representações de criatividade e a resolução criativa de problemas em jovens, tem sido um dos mais implementados. Os seus materiais e atividades foram adaptados para estudantes portugueses, efetuando-se um estudo longitudinal. O programa foi implementado durante quatro meses, semanalmente, por treze professores, que receberam formação antes e durante a implementação. O grupo experimental incluiu 77 estudantes do Ensino Básico e Secundário, apresentando o grupo de controlo 78 estudantes com características equivalentes. Os dados sobre a motivação e criatividade foram recolhidos num pré e pós-teste. Os resultados sugerem um aumento significativo na motivação e crenças apropriadas de criatividade no grupo experimental. Implicações práticas e perspectivas para investigações futuras são apresentadas.La creatividad y su promoción generan gran preocupación en educación. Sin embargo, han sido llevados a cabo pocos esfuerzos para implementar programas de promoción de la creatividad y otros aspectos (e.g., motivación académica). El Future Problem Solving Program International (FPSPI), creado para mejorar las representaciones de creatividad y la solución creativa de problemas en jóvenes, ha sido bastante implementado. Se adaptaron sus materiales y actividades para estudiantes portugueses, y se desarrolló un estudio longitudinal. El programa se implementó semanalmente durante cuatro meses por trece profesores, que recibieron formación antes y durante la implementación. El grupo experimental incluyó 77 estudiantes de Educación Primaria y Secundaria y el grupo de control incluyó 78 estudiantes con características semejantes. Los datos de motivación y creatividad fueron recogidos en un pre y post-test, sugiriendo un aumento significativo de motivación y creencias apropiadas sobre la creatividad en el grupo experimental. Se presentan implicaciones prácticas y perspectivas para futuras investigaciones.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BPD/80825/201

Lee Silverman Voice Treatment versus standard speech and language therapy versus control in Parkinson’s disease: a pilot randomised controlled trial (PD COMM pilot)

Background: Speech-related problems are common in Parkinson’s disease (PD), but there is little evidence for the effectiveness of standard speech and language therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUD®). Methods: The PD COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT) of LSVT LOUD®, SLT and no intervention (1:1:1 ratio) to assess the feasibility and to inform the design of a full-scale RCT. Non-demented patients with idiopathic PD and speech problems and no SLT for speech problems in the past 2 years were eligible. LSVT LOUD® is a standardised regime (16 sessions over 4 weeks). SLT comprised individualised content per local practice (typically weekly sessions for 6–8 weeks). Outcomes included recruitment and retention, treatment adherence, and data completeness. Outcome data collected at baseline, 3, 6, and 12 months included patient-reported voice and quality of life measures, resource use, and assessor-rated speech recordings. Results: Eighty-nine patients were randomised with 90% in the therapy groups and 100% in the control group completing the trial. The response rate for Voice Handicap Index (VHI) in each arm was ≥ 90% at all time-points. VHI was highly correlated with the other speech-related outcome measures. There was a trend to improvement in VHI with LSVT LOUD® (difference at 3 months compared with control: − 12.5 points; 95% CI − 26.2, 1.2) and SLT (difference at 3 months compared with control: − 9.8 points; 95% CI − 23.2, 3.7) which needs to be confirmed in an adequately powered trial. Conclusion: Randomisation to a three-arm trial of speech therapy including a no intervention control is feasible and acceptable. Compliance with both interventions was good. VHI and other patient-reported outcomes were relevant measures and provided data to inform the sample size for a substantive trial