Viral load and lymphocyte subpopulations in newly diagnosed patients with chronic Hepatitis B

INTRODUCTION: The immune response against Hepatitis B virus (HBV) represents a key factor for infection outcome. However, the relation between viral replication and host immune reactivity is still a matter of investigation. AIM: To investigate whether the cellular immune response of newly diagnosed treatment naïve chronic hepatitis B (CHB) patients may be influenced by the replicative status of HBV.MATERIALS AND METHODS: A total of 45 (17 female and 28 male) newly diagnosed untreated CHB patients aged 42.48±13.19 years (19÷71 years) were enrolled in this study. The patients were divided in two groups according to the viral load: >0÷≤104 copies/ml (n=25) and >10 4÷<108 copies/ml (n=17). Flowcytometric immunophenotyping was performed for evaluation of the cellular immunity. Serum HBV DNA load was assessed by quantitative real-time polymerase chain reaction.RESULTS: Similar alterations were observed in both patients` groups in comparison with healthy controls which could be summarized as follows: decreased total T cells (CD3+) due to low helper-inducer (CD3+CD4+) and suppressor-cytotoxic (CD3+CD8+) subpopulations; reduced effector cytotoxic (CD8+CD11b-; CD8+CD28+) and activated (CD3+HLA-DR+, CD8+CD38+) T-cell subsets; increased CD57+CD8- cells; elevated percentage of B lymphocytes. No significant differences in the studied immune parameters were detected between both patients` groups except the significantly elevated CD4/CD8 ratio in individuals with higher in comparison to those with lower HBV DNA levels.CONCLUSION: Alterations in the cellular immune repertoire of CHB patients were observed resulting mainly in significantly decreased T-cell subpopulations, particularly those with effector cell immune phenotype regardless of the viral load

Comunitat amigable per a les persones amb demència. Fem-ho possible!

&#091;cat&#093; Aquest capítol pretén justificar la necessitat de crear una comunitat conscienciada, respectuosa i facilitadora de la inclusió social de les persones afectades per diferents tipus de demències, partint de la hipòtesi que aquestes iniciatives produeixen beneficis en la qualitat de vida de les persones, les seves famílies cuidadores i la societat. En primer lloc, exposem un recull de les experiències i els models d’intervenció que s’han fet en l’àmbit internacional i nacional, així com un seguiment dels procediments per implementar aquestes comunitats. A continuació, presentem l’experiència i els primers resultats recollits després de la posada en marxa, per part de la Creu Roja, en col·laboració amb altres entitats, d’un projecte pilot d’enfocament comunitari. El projecte, basat en els models explorats i l’estudi de necessitats en l’àmbit local, pretén crear espais amigables amb la demència en diferents barris de la ciutat de Palma. Finalment, emmarquem la iniciativa de la creació de la Comunitat Amigable amb la Demència en la línia d’actuació de l’Ajuntament de Palma com a membre de la Xarxa Espanyola de Ciutats i Comunitats Amigables amb la Gent Gran.&#091;spa&#093; Este capítulo pretende justificar la necesidad de crear una comunidad concienciada, respetuosa y facilitadora de la inclusión social de las personas afectadas por diferentes tipos de demencias, partiendo de la hipótesis que iniciativas de este tipo producen beneficios en la calidad de vida de estas personas, sus familias cuidadoras y la sociedad. En primer lugar, exponemos una recopilación de las experiencias y los modelos de intervención que se han realizado a nivel internacional y nacional, así como un seguimiento de los procedimientos para implementar dichas comunidades. A continuación, presentamos la experiencia y los primeros resultados recogidos después de la puesta en marcha, por parte de Cruz Roja en colaboración con otras entidades, de un proyecto piloto de enfoque comunitario. El proyecto, basado en los modelos explorados y el estudio de necesidades a nivel local, pretende crear espacios amigables con la demencia en diferentes barrios de Palma. Finalmente, enmarcamos la iniciativa de la creación de la Comunidad Amigable con la Demencia dentro de la línea de actuación del Ayuntamiento de Palma como miembro de la Red Española de Ciudades y Comunidades Amigables con las Personas Mayores

How Can the EU Beating Cancer Plan Help in Tackling Lung Cancer, Colorectal Cancer, Breast Cancer and Melanoma?

Cancer is the second leading cause of mortality in EU countries, and the needs to tackle cancer are obvious. New scientific understanding, techniques and methodologies are opening up horizons for significant improvements in diagnosis and care. However, take-up is uneven, research needs and potential outstrip currently available resources, manifestly beneficial practices—such as population-level screening for lung cancer—are still not generalised, and the quality of life of patients and survivors is only beginning to be given attention it merits. This paper, mainly based on a series of multistakeholder expert workshops organised by the European Alliance for Personalised Medicine (EAPM), looks at some of those specifics in the interest of planning a way forward. Part of this exercise also involves taking account of the specific nature of Europe and its constituent countries, where the complexities of planning a way forward are redoubled by the wide variations in national and regional approaches to cancer, local epidemiology and the wide disparities in health systems. Despite all the differences between cancers and national and regional resources and approaches to cancer care, there is a common objective in pursuing broader and more equal access to the best available care for all European citizens

How Can the EU Beating Cancer Plan Help in Tackling Lung Cancer, Colorectal Cancer, Breast Cancer and Melanoma?

Cancer is the second leading cause of mortality in EU countries, and the needs to tackle cancer are obvious. New scientific understanding, techniques and methodologies are opening up horizons for significant improvements in diagnosis and care. However, take-up is uneven, research needs and potential outstrip currently available resources, manifestly beneficial practices—such as population-level screening for lung cancer—are still not generalised, and the quality of life of patients and survivors is only beginning to be given attention it merits. This paper, mainly based on a series of multistakeholder expert workshops organised by the European Alliance for Personalised Medicine (EAPM), looks at some of those specifics in the interest of planning a way forward. Part of this exercise also involves taking account of the specific nature of Europe and its constituent countries, where the complexities of planning a way forward are redoubled by the wide variations in national and regional approaches to cancer, local epidemiology and the wide disparities in health systems. Despite all the differences between cancers and national and regional resources and approaches to cancer care, there is a common objective in pursuing broader and more equal access to the best available care for all European citizens

How Can the EU Beating Cancer Plan Help in Tackling Lung Cancer, Colorectal Cancer, Breast Cancer and Melanoma?

Cancer is the second leading cause of mortality in EU countries, and the needs to tackle cancer are obvious. New scientific understanding, techniques and methodologies are opening up horizons for significant improvements in diagnosis and care. However, take-up is uneven, research needs and potential outstrip currently available resources, manifestly beneficial practices—such as population-level screening for lung cancer—are still not generalised, and the quality of life of patients and survivors is only beginning to be given attention it merits. This paper, mainly based on a series of multistakeholder expert workshops organised by the European Alliance for Personalised Medicine (EAPM), looks at some of those specifics in the interest of planning a way forward. Part of this exercise also involves taking account of the specific nature of Europe and its constituent countries, where the complexities of planning a way forward are redoubled by the wide variations in national and regional approaches to cancer, local epidemiology and the wide disparities in health systems. Despite all the differences between cancers and national and regional resources and approaches to cancer care, there is a common objective in pursuing broader and more equal access to the best available care for all European citizens.publishedVersionPeer reviewe

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

NUTRIGENETIC TESTS FOR LIFE-STYLE OPTIMIZATION IN THE BULGARIAN POPULATION - DIFFICULTIES, ADVANCES AND FUTURE PERSPECTIVES

Introduction: Nutrigenetics is a relatively new, but intensively developing scientific field. It aims to improve the quality of life by customizing dietary intake, physical activity and environmental exposures according to the personal genetic variantions.Aim: The aim of the study is to examine the attitude of the Bulgarian society towards nutrigenetic tests and how knowledge of personal genetic data influences current lifestyle choices.Materials and Methods: Seventy-eight Bulgarian probands were tested for the 56 single nucleotide polimorphisms (SNPs) in 52 genes, related to the lipid, carbohydrate, vitamin B and D metabolism, inflammation, oxidative stress, osteoporosis detoxification, PUFA, caffeine and salt responsiveness, predisposition to tendon injuries, as well as genes associated with power and endurance in athletes (DNA Life, Nordic Laboratories). Each proband provided a written informed consent before testing, as well as filled in questionnaires as part of pre-test counseling and then a few months later. Each patient was consulted by a trained genetic counselor. Probands were provided with detailed information about the test, detected polymorphic variants and personalized recommendations for diet, sport and lifestyle changes.Results: The preliminarily results reveal that large portion of the respondents could directly follow the received personal recommendations. In a small number of the patients a chronic disease during the counseling was detected and they were directed to the gastroenterologist for treatment. A significant share of our cohort, found to be predisposed to obesity, insulin resistance and osteoporosis, has already manifested some symptoms and the individuals were referred to a dietitian and endocrinologist, respectively. Patient follow-up, as well as data collection from the questionnaires are ongoing.Conclusion: This study shows that Bulgarians are inclined to do nutrigenetic tests for prevention of socially significant disorders and stresses the need for a trained physician to analyze test results and offer the most suitable lifestyle modifications in order to minimize morbidity risk

IgM-mediated autoimmune responses directed against multiple neoepitopes in depression : new pathways that underpin the inflammatory and neuroprogressive pathophysiology

BioEM ; BioELECInternational audienceBACKGROUND: There is evidence that depression is accompanied by oxidative and nitrosative stress (O&NS), as indicated by increased free radical levels, lipid peroxidation, and lowered antioxidant levels. The aims of the present study are to examine whether depression is accompanied by autoimmune responses directed against a) neoepitopes that are formed following O&NS damage; and b) the major anchorage molecules, i.e. palmitic and myristic acids and S-farnesyl-L-cysteine. METHODS: We examined serum IgM antibodies to the conjugated fatty acids, palmitic and myristic acids; acetylcholine; S-farnesyl-L-cysteine; and NO-modified adducts in 26 depressed patients and 17 normal controls. Severity of depression was measured with the Hamilton Depression Rating Scale and severity of fatigue and somatic (F&S) symptoms with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. RESULTS: The prevalences and mean values for the serum IgM levels directed against conjugated palmitic and myristic acids, acetylcholine, S-farnesyl-L-cysteine; and the conjugated NO adducts, NO-tyrosine, NO-phenylalanine, NO-aspartate, NO-histidine, and NO-creatine were significantly higher in depressed patients than in normal controls. The autoimmune responses were significantly related to FF symptoms, such as fatigue and a flu-like malaise, whereas the indicants of nitrosative stress were related to gastro-intestinal and autonomic symptoms. DISCUSSION: Depression is characterized by IgM-related autoimmune responses directed against a) neoepitopes that are normally not detected by the immune system but that due to damage by O&NS have become immunogenic; and b) anchorage epitopes, i.e. palmitic and myristic acids, and S-farnesyl-L-cysteine. These autoimmune responses play a role in the inflammatory and O&NS pathophysiology of depression and may mediate the cellular dysfunctions that contribute to neuroprogression, e.g. aberrations in signal transduction, cellular differentiation and apoptosis

Lower whole blood glutathione peroxidase (GPX) activity in depression, but not in myalgic encephalomyelitis / chronic fatigue syndrome: another pathway that may be associated with coronary artery disease and neuroprogression in depression

BAKGROUND: Major depression and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are two disorders accompanied by an upregulation of the inflammatory and oxidative and nitrosative (IO&amp;NS) pathways and a decreased antioxidant status. Moreover, depression is accompanied by disorders in inflammatory and neuroprogressive (IN-PRO) pathways. METHODS: This study examines whole blood glutathione peroxidase (GPX) in depression and in ME/CFS; GPX is an enzyme that reduces hydroperoxides by oxidizing glutathione and consequently protects the cells from oxidative damage. Blood was sampled in 39 patients with depression, 40 patients with ME/CFS and 24 normal volunteers. Whole blood was analysed for GPX activity using the Ransel assay (Randox). Severity of illness was measured by means of the Hamilton Depression Rating Scale (HDRS) and the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (FF scale). RESULTS: We found that whole blood GPX activity was significantly (p=0.001) lower in depressed patients than in normal controls and that there were no significant differences between ME/CFS and controls. In depression and ME/CFS, there were significant and inverse relationships between GPX activity and the FF items, depressed mood and autonomic symptoms. In depression, there were significant and negative correlations between whole blood GPX and the HDRS score and autonomic symptoms. DISCUSSION: The results show that lowered whole blood GPX activity contributes to the lowered antioxidant status in depression. Since GPX activity is a predictor of neuroprogression and coronary artery disease (CAD), lowered GPX activity in depression contributes to the IN-PRO pathways and the comorbidity between depression and CAD. Our results suggest that patients with depression would benefit from Ebselen or a supplementation with glutathione, N-Acetyl-l-Cysteine and selenium. <br /