Accessible health care for Roma: a gypsy's tale a qualitative in-depth study of access to health care for Roma in Ghent

Background: In general, vulnerable populations experience more problems in accessing health care. This also applies to the Roma-population. In the City of Ghent, Belgium, a relativly large group of Roma resides more or less permanently. The aim of this study is to explore the barriers this population encounters in their search for care. Methods: In this qualitative study using in-depth interviews the barriers to health care for the Roma in Ghent are explored. We interviewed 12 Roma and 13 professionals (volunteers, health care providers,.) who had regular contact with the Roma-population in Ghent. For both groups purposive sampling was used to achieve maximal variation regarding gender, age, nationality and legal status. Results: The Roma-population in Ghent encounters various barriers in their search for care. Financial constraints, not being able to reach health care and having problems to get through the complexity of the system are some of the most critical problems. Another important finding is the crucial role of trust between patient and care provider in the care-giving process. Conclusion: Roma share several barriers with other minority groups, such as: financial constraints, mobility issues and not knowing the language. However, more distinctive for this group is the lack of trust in care providers and health care in general. As a result, restraint and lack of communication form serious barriers for both patient and provider in their interaction. In order to ensure equitable access for Roma, more emphasis should be on establishing a relationship of mutual respect and understanding

Implication de la glutamine dans l'activation de mTORC1 dans les leucémies aiguës myéloïdes et inhibition ciblée

Dans les leucémies aiguës myéloïdes (LAM), l activation anormale de nombreuses voies de signalisation intracellulaires favorise la croissance et la survie des cellules tumorales. L amélioration des connaissances biologiques de ces pathologies hétérogènes, dont le pronostic est réservé, devrait permettre le développement de thérapies ciblées. La kinase oncogénique mTOR est présente au sein de deux complexes, parmi lesquels mTORC1, activé constitutivement dans la majorité des blastes primaires de patients porteurs de LAM, qui contrôle la synthèse protéique, et mTORC2 activé constitutivement dans 50% des LAM. Les inhibiteurs allostériques de mTORC1 (la rapamycine et ses dérivés) n inhibent pas la phosphorylation du répresseur traductionnel 4E-BP1, ne diminuent pas la traduction et induisent peu d apoptose in vitro dans les LAM. Utilisés en monothérapie, leur effet est décevant. De plus ces inhibiteurs n agissent pas sur le complexe mTORC2. J ai étudié l effet d un inhibiteur catalytique de mTOR, l AZD8055, actif sur les deux complexes. In vitro, l AZD8055 inhibe efficacement la signalisation en aval de mTORC1 et de mTORC2, dont les sites de phosphorylation de 4E-BP1 résistants à la rapamycine, ainsi que la synthèse protéique. Il diminue la prolifération, bloque le cycle cellulaire en phase G0G1 et induit une apoptose caspase-dépendante dans les blastes primaires de LAM. Il diminue également la clonogénicité des progéniteurs leucémiques, sans affecter celle des cellules CD34+ normales. Dans un modèle murin de xéno-transplantation, l AZD8055 inhibe la croissance tumorale et améliore la survie des souris traitées. Je me suis également intéressée à la régulation de l activité de mTORC1 par les acides aminés. Dans les cellules de mammifères, l activation de mTORC1 nécessite la présence de glutamine et de leucine qui agissent en coopération via deux transporteurs membranaires, SLC1A5 et SLC7A5/SLC3A2. J ai montré que la privation en glutamine, obtenue par l activité glutaminase de la drogue L-asparaginase ou par l utilisation de milieux de culture spécifiques dépourvus sélectivement en acides aminés, inhibe l activation de mTORC1 et induit de l apoptose dans diverses lignées leucémiques et dans les blastes primaires de LAM. La L-asparaginase inhibe la synthèse protéique et ses effets fonctionnels sont liés à son activité glutaminase. J ai pu également constater une augmentation de l expression protéique de la glutamine synthase induite par la Lasparaginase, dont l inhibition majore l apoptose induite par la L-asparaginase dans certaines lignées leucémiques. J ai également étudié l effet de l inhibition spécifique par un shARN inductible du transporteur SLC1A5, qui permet l import de glutamine. L inhibition de SLC1A5 bloque la réactivation de mTORC1 par l association leucine/glutamine après privation et induit de l apoptose dans la lignée leucémique MOLM14. Cette inhibition diminue la croissance tumorale dans un modèle de xénogreffeAcute myeloid leukaemias (AML) are heterogeneous diseases associated with poor prognosis. In AML, aberrant activation of many signaling pathways enhances proliferation and survival of leukemic blast cells. Understanding the mechanisms underlying survival of tumoral cells should allow the development of targeted therapies. The oncogenic kinase mTOR belongs to two distinct multimeric complexes. MTORC1 that controls protein translation, is constitutively activated in most of primary blast cells at AML diagnosis, while mTORC2 is constitutively activated in about half of AML samples. In AML, some phosphorylation events of the translational repressor 4E-BP1, are resistant to allosteric inhibitors of mTORC1 including rapamycin and its analogs. These first generation inhibitors of mTORC1 have only few effects on AML and do not induce significant apoptosis in vitro. I have tested a second generation mTOR kinase inhibitor active on both mTORC1 and mTORC2 complexes. In vitro, AZD8055 blocked mTORC1 and mTORC2 signaling, including 4E-BP1 rapamycin resistant phosphorylation events and protein synthesis. This compound decreased AML blast cells proliferation and cell cycle progression, reduced the clonogenic growth of leukemic progenitors and induced caspase-dependant apoptosis in leukemic cells but not in normal immature CD34+ cells. Finally, AZD8055 reduced tumor growth and improved survival in xenografted mouse model. In the second part of this work, I have studied the regulation of mTORC1 by amino acids in AML. In mammalian cells, activation of mTORC1 requires the presence of glutamine and leucine acting together via two membrane transporters, SLC1A5 and SLC7A5/SLC3A2. I showed that glutamine deprivation, obtained by L-asparaginase glutaminase activity or specific alpha-MEM use, inhibited mTORC1 and induced apoptosis in AML cell lines and primary AML blasts. L-asparaginase also inhibited protein synthesis and I have observed a correlation between the functional effects of L-asparaginase and its glutaminase activity. L-asparaginase induced an up-regulation of glutamine synthase (GS) protein and shRNA-induced GS inhibition increased L-asparaginase-dependant apoptosis in the MV4-11 AML cell line. I have also studied the effects of SLC1A5 inhibition with an inducible shRNA expressed in MOLM14 cells. Inhibition of this high afffinity transporter for glutamine blocked mTORC1 stimulation by leucine and glutamine after deprivation and induced apoptosis in MOLM-14 cell line. SLC1A5 inhibition reduced tumor growth and improved survival in transplanted micePARIS5-Bibliotheque electronique (751069902) / SudocSudocFranceF

Onderzoeksrapport 'Gezondheidsprofiel gedetineerden'

Het onderzoeksproject ‘Gezondheidsprofiel van gedetineerden’ heeft als doel het gezondheidsprofiel bij gedetineerden in Vlaamse en Brusselse gevangenissen kwantitatief te beschrijven. Hiertoe is bij een representatieve steekproef van 817 gedetineerden in 12 geselecteerde gevangenissen informatie verzameld over hun gezondheid, gezondheidsgedrag en gezondheidsdeterminanten. De verzamelde gegevens illustreren dat gedetineerden voor de meeste gezondheidsproblemen en gezondheidsgedragingen slechter scoren dan de algemene populatie

Primary care for the Roma in Europe : position paper of the European forum for primary care

Roma populations’ low health status and limited access to health services, including primary care, has been documented in many European countries, and warrants specific health policies and practices. A variety of experiences shows how primary care can adjust its practices to reduce the barriers to primary care for Roma populations. At local level, establishing collaboration with Roma organisations helps primary care to improve mutual relations and quality of care. Mediation has proved to be an effective tool. Skills training of primary care practitioners may enhance their individual competences. Research and international sharing of experiences are further tools to improve primary care for the Roma people

Skin Microvascular Thrombosis in Fusarium Infection in Two Early Biopsied Cases

Fusarium species cause rare and severe infections. Their incidence is increasing in immunocompromised patients but they are also observed in healthy hosts. Because of the rapid dissemination of infection and the frequent resistance of Fusarium species to antifungal drugs, histopathologic evidence of hyphae is very helpful to obtain the diagnosis rapidly. We report the clinical and pathological features of two patients with initial cutaneous lesions. Cutaneous early biopsies showed microvessel involvement with hyphae and thrombosis. Fusarium infection was confirmed by skin culture. Hyphae within a microvessel thrombus in the skin were highly suggestive of disseminated fungal infection. These pathological features enabled to establish an early diagnosis and to start efficient antifungal treatment. In early cutaneous biopsies of immunocompromised patients, the presence of cutaneous vessel thrombosis can suggest a fungal infection and may help to start specific therapy without delay for these life-threatening infections

Online consultations in mental healthcare: Modelling determinants of use and experience based on an international survey study at the onset of the pandemic

Introduction: While online consultations have shown promise to be a means for the effective delivery of high -quality mental healthcare and the first implementations of these digital therapeutic contacts go back nearly two decades, uptake has remained limited over the years. The onset of the COVID-19 pandemic dramatically altered this relative standstill and created a unique turning point, with a massive amount of both professionals and clients having first hands-on experiences with technology in mental healthcare.Objective: The current study aimed to document the uptake of online consultations and explore if specific characteristics of mental health professionals across and beyond Europe could predict this.Methods: An international survey was designed to assess mental health professionals' (initial) experiences with online consultations at the onset of the pandemic: their willingness to make use of them and their prior and current experiences, alongside several personal characteristics. Logistic mixed-effects models were used to identify predictors of the use of online consultations, personal experience with this modality, and the sense of telepresence.Results: A total of 9115 healthcare professionals from 73 countries participated of which about two-thirds used online consultations during the initial COVID-19 outbreak. The current study identifies multiple determinants relating to the use and experience of online consultations, including the professionals' age, experience with the technology before the outbreak, the professional context, and training.Conclusions: Despite strong evidence supporting the relevance of training in digital mental health, this is clearly still lacking. Nevertheless, the COVID-19 pandemic presented a first, and potentially transformative, experience with online consultations for many healthcare professionals. The insights from this study can help supportprofessionals and, importantly, (mental) healthcare organisations to create optimal circumstances for selective and high-quality continued use of online consultations

Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity and Insulin Resistance

Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.acceptedVersio

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Throug