Les arboviroses tropicales émergentes en France (dengue et chikungunya) : étude du rôle du pharmacien d'officine dans la lutte anti-vectorielle (Thèse d'exercice de Pharmacie)

En 2005, l’épidémie de chikungunya qui a sévi sur l’île de la Réunion a marqué les esprits. Depuis, avec l’arrivée d’un moustique pouvant être le vecteur de cette maladie en France ; Aedes albopictus, la problématique s’est élargie. Venu initialement d’Italie, ce moustique se propage en effet le long du littoral méditerranéen français et peut véhiculer les virus de la dengue et du chikungunya pour les transmettre à l’homme. Pour éviter l’émergence de ces arboviroses, il faut donc lutter contre le moustique tigre sous deux aspects : l’aspect de la nuisance mais aussi et surtout, l’aspect de sa capacité et de sa compétence vectorielle. Les différents messages de la lutte anti-vectorielle peuvent apparaître ambigus et leur utilité est parfois remise en question. Ainsi, le pharmacien est un acteur de santé incontournable, sollicité par les populations des régions endémiques pour disposer de plus d’informations et savoir comment se protéger contre Aedes albopictus. Une étude a donc été réalisée pour réaliser un état des lieux des connaissances des pharmaciens d’officine dans ce domaine, dans la ville de Marseille. Or, les enseignements tirés de cette enquête ont été la mise en évidence des lacunes pouvant porter préjudice à la bonne information et donc éducation communautaire. Un plan d’actions est donc proposé pour améliorer la prise en charge

D2 or non D2-lymphadenectomy in gastric cancer

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Gastric cancer: predictors of recurrence when lymph-node dissection is inadequate

<p>Abstract</p> <p>Background</p> <p>The TNM classification (sixth edition) requires at least 15 lymph nodes to be examined to allow an accurate staging. However, in our environment, only 20% of patients have the recommended minimum of 15 nodes removed.</p> <p>Purpose</p> <p>To evaluate clinicopathological predictors of recurrence in patients with gastric cancer undergoing radical resection with an inadequate number of lymph nodes examined.</p> <p>Methods</p> <p>101 patients were included in this retrospective cohort. We evaluated age, gender, tumoral location, Borrmann type, Lauren histotype, type of gastrectomy, grade, invasion depth of tumor, lymph node involvement, ratio between metastatic and total number of excised lymph nodes keeping 20% as the cutoff value (LNR) and adjuvant treatment. The association between these variables and recurrence was investigated by using univariate methods and multivariate logistic regression analysis.</p> <p>Results</p> <p>Median (range) age was 63 years (44-85). 63% males, 37% females. Median follow-up time for the whole patients population was 36 months (10-104). Median number of lymph nodes retrieved was 6 (0-14). Recurrence: 50 of 101 cases (49,6%); 41 hematogeneus dissemination, 9 locoregional recurrences. The following factors were found to be correlated with the recurrence risk: tumoral location, invasion depth of tumor, lymph node involvement and LNR. A multivariate analysis revealed that depth of invasion [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.03-7.58, P = 0.04] and LNR (OR 2.34, 95% CI 1.05-5.21, P = 0.03) were independent risk factors for recurrences of gastric cancer. Median time to recurrence: 16 months (2-50). 82% of recurrences occurred within the first two years after surgical treatment. The estimated cumulative risk of recurrence at five years: 61% in the whole patients population, with serosal invasion and LNR > and < 20% was 82% and 44%, without serosal invasion 73% and 39% respectively.</p> <p>Conclusion</p> <p>Invasion depth of tumor and LNR were independent predictors of recurrence in gastric cancer after potentially curative resection with an inadequate number of lymph nodes examined.</p

Relationships between crystalline structure and dielectric properties in Sr2Sm(1-x)NdxTi2Nb3O15 ceramics

In this study, tungsten-bronze type materials of Sr2Sm(1-x)NdxTi2Nb3O15 composition (x=0; 0,25; 0,5; 0,75 and 1) were elaborated by classical solid-state reaction. The structural characterization demonstrate that these compounds present tetragonal symmetry, using two space groups P4bm (N°100) and P4/mbm (N°127) respectively. The lattice parameters are a=b≈12,2Ǻ; c≈3,8Ǻ; V≈579,03Ǻ and Z=2. In this compounds, Ti and Nb cations show obvious off-center displacements along the c axis in both the Ti/Nb(1)O6 and the Ti/Nb(2)O6 octahedra. Besides, the unequal Ti/Nb(2)–O bonds length in the equatorial plane of Ti/Nb(2)O6 octahedra indicates the displacement of the Ti/Nb(2) cations in the ab plane, and no displacement of the Ti/Nb(1) cations exists in the ab plane. The results show that this material has two types of octahedral, first octahedron with little deformation around the Ti1/Nb1 and the second octahedron are more distorted around the Ti2/Nb2. The measurements of permittivity and dielectric losses of the ceramic samples performed between 25°C and 700°C (100Hz to 1MHz), high dielectric constants (εr=127 ~ 194) and low dielectric losses (tan(δ) around 10-4 at 1MHz) were found. The maximum value of the dielectric constant is obtained for x=0 (εr=194). The Curie temperature Tc decreases from 332 to 246°C as a function of the substitution of the samarium by neodymium. Detailed microstructural analysis by scanning electron microscope (SEM) and (EDS) for this compounds are also investigated

Metachronous hepatic metastases from gastric carcinoma: a multicentric survey

BACKGROUND: The treatment of hepatic metastases from gastric cancer is controversial, due to biologic aggressiveness of the disease. OBJECTIVE: To survey the clinical approach to the subset of atients presenting with metachronous hepatic metastases as sole site of recurrence after curative resection of gastric cancer, focusing on the results achieved by different therapies and to investigate the prognostic factors of major clinical relevance. METHODS: Retrospective multi-center chart review evaluating 73 patients, previously submitted to D >or= 2 gastrectomy for gastric cancer, who developed exclusive hepatic recurrence. Prognostic factors related to the patient, to the gastric malignancy and its treatment, and to the metastatic disease and its therapy were evaluated. RESULTS: Forty-five patients received supportive care, 17 were submitted to chemotherapy, and 11 to hepatic resection. Survival was independently influenced by the variables T (p=0.019), N (p=0.05) and G (p=0.018) of the gastric primary and by the therapeutic approach to the metastases (p<0.005). In particular, T4 gastric cancer, presence of lymph-node metastases and G3 tumor displayed a negative prognostic value. Therapeutic approach to the metastases was the principal prognostic variable: 1, 2, and 3 years survival rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific treatment; 44.9%, 12.8% and 6.4% after chemotherapy (p=0.08) and 80.8%, 30.3% and 20.2% after surgical resection (p<0.001). CONCLUSIONS: Our data suggest some clinical criteria that may facilitate selection of therapy for patients with hepatic recurrence after primary gastric cancer resection. The best survival rates are associated with surgical treatment, which should be chosen whenever possible

Using digital social market applications to incentivise active travel: Empirical analysis of a smart city initiative

Information and communication technologies (ICTs), such as mobile communication networks, and behaviour-based approaches for citizen engagement play a key role in making future cities sustainable and tackling persistent problems in high-density urban areas. In the context of Sharing Cities, an EU-funded programme aiming to deliver smart city solutions in areas such as citizen participation and infrastructure improvements of buildings and mobility, a prominent intervention has been the deployment and monitoring of a Digital Social Market (DSM) tool in Milan (Italy). The DSM allows cities to engage with residents and encourage sustainable behaviours by offering non-monetary rewards. This paper aims to evaluate the effectiveness of the DSM approach to promote active travel (cycling and walking) by analysing the data collected through the app as well as through participant surveys. Our model results show that a broader engagement with the DSM app (number of claps to posts, number of posts made, non-monetary rewards earned by participating in non-travel events) is positively correlated with the monitored level of active travel. Lifestyles, attitudes, and social influence also explain the variability in cycling and walking. This highlights the importance of investigating these factors when replicating such initiatives on a large scale

Targeting Multiple Mitochondrial Processes by a Metabolic Modulator Prevents Sarcopenia and Cognitive Decline in SAMP8 Mice

The age-dependent declines of skeletal muscle and cognitive functions often coexist in elderly subjects. The underlying pathophysiological mechanisms share common features of mitochondrial dysfunction, which plays a central role in the development of overt sarcopenia and/or dementia. Dietary supplementation with formulations of essential and branched-chain amino acids (EAA-BCAA) is a promising preventive strategy because it can preserve mitochondrial biogenesis and function. The senescence-accelerated mouse prone 8 (SAMP8) is considered an accurate model of age-related muscular and cognitive alterations. Hence, we aimed to investigate the progression of mitochondrial dysfunctions during muscular and cognitive aging of SAMP8 mice and to study the effects of a novel EAA-BCAA-based metabolic modulator on these changes. We evaluated body condition, motor endurance, and working memory of SAMP8 mice at 5, 9, 12, and 15 months of age. Parallel changes in protein levels of mitochondrial respiratory chain subunits, regulators of mitochondrial biogenesis and dynamics, and the antioxidant response, as well as respiratory complex activities, were measured in the quadriceps femoris and the hippocampus. The same variables were assessed in 12-month-old SAMP8 mice that had received dietary supplementation with the novel EAA-BCAA formulation, containing tricarboxylic acid cycle intermediates and co-factors (PD-0E7, 1.5 mg/kg/body weight/day in drinking water) for 3 months. Contrary to untreated mice, which had a significant molecular and phenotypic impairment, PD-0E7-treated mice showed preserved healthy body condition, muscle weight to body weight ratio, motor endurance, and working memory at 12 months of age. The PD-0E7 mixture increased the protein levels and the enzymatic activities of mitochondrial complex I, II, and IV and the expression of proliferator-activated receptor \u3b3 coactivator-1\u3b1, optic atrophy protein 1, and nuclear factor, erythroid 2 like 2 in muscles and hippocampi. The mitochondrial amyloid-\u3b2-degrading pitrilysin metallopeptidase 1 was upregulated, while amyloid precursor protein was reduced in the hippocampi of PD-0E7 treated mice. In conclusion, we show that a dietary supplement tailored to boost mitochondrial respiration preserves skeletal muscle and hippocampal mitochondrial quality control and health. When administered at the early onset of age-related physical and cognitive decline, this novel metabolic inducer counteracts the deleterious effects of precocious aging in both domains

AAV-mediated liver-specific MPV17 expression restores mtdna levels and prevents diet-induced liver failure

Mutations in human MPV17 cause a hepatocerebral form of mitochondrial DNA depletion syndrome (MDS) hallmarked by early-onset liver failure, leading to premature death. Liver transplantation and frequent feeding using slow-release carbohydrates are the only available therapies, although surviving patients eventually develop slowly progressive peripheral and central neuropathy. The physiological role of Mpv17, including its functional link to mitochondrial DNA (mtDNA) maintenance, is still unclear. We show here that Mpv17 is part of a high molecular weight complex of unknown composition, which is essential for mtDNA maintenance in critical tissues, i.e. liver, of a Mpv17 knockout mouse model. On a standard diet, Mpv17(-/-) mouse shows hardly any symptom of liver dysfunction, but a ketogenic diet (KD) leads these animals to liver cirrhosis and failure. However, when expression of human MPV17 is carried out by adeno-associated virus (AAV)-mediated gene replacement, the Mpv17 knockout mice are able to reconstitute the Mpv17-containing supramolecular complex, restore liver mtDNA copy number and oxidative phosphorylation (OXPHOS) proficiency, and prevent liver failure induced by the KD. These results open new therapeutic perspectives for the treatment of MPV17-related liver-specific MDS