Étude de l'angiogénèse et développement d'un modèle animal pour l'étude du sarcome de Kaposi

La progression du virus du SIDA chez l'humain a atteint une telle proportion qu'aucune classe de la société n'est à l'abri. L'avènement du SIDA a causé une incidence plus élevée de certaines pathologies, comme le sarcome de Kaposi (SK). Il s’agit d’un cancer des cellules endothéliales, pour lequel aucun modèle expérimental n’existait. Nous avons développé, dans le cadre de nos recherches, un modèle de souris qui mime en partie les conditions rencontrées chez les patients sidéens souffrant du SK. Puisqu'il s'agissait d'une néoplasie des cellules endothéliales, nos recherches ont été dirigées vers des traitements antiangiogéniques. La première partie de l'étude a été effectuée sur l'angiogénèse, et consistait en des traitements apposés à la surface de la membrane chorio-allantoïdienne (CAM). Nous avons utilisé le tétraHydro S ainsi que le 17?-hydroxyprogestérone combiné au MTP déposés en forme de disque à la surface de la CAM. Nous avons obtenu des zones avasculaires confirmant leur activité. La combinaison MTP-tétrahydro S a donné les meilleurs résultats. La seconde partie contient l'objectif principal de cette recherche. Trente semaines d'injections hebdomadaires s.c. de DMH chez des souris C57BI/6 mâles induisent I’apparition d'angiosarcomes dans 80 % des cas. Nous avons augmenté I’immunosuppression de ces souris en utilisant le virus LP-BM5. Les paramètres immunitaires ont été étudiés à l'aide: de stimulation en présence de Con A ou de LPS, de la réponse PFC et d'un dénombrement lymphocytaire du sang et de la rate

Changes in Photosynthate Unloading from Perfused Seed Coats of Phaseolus vulgaris L Induced by Osmoticum and Ethylenediaminetetraacetate (EDTA)

ABSTRACT Photosynthate unloading in Phaseolus vulgaris L. seed coats was studied by treating perfused seed coats with differing concentrations of an osmoticum and ethylenediaminetetraacetate (EDTA). Large changes in osmoticum concentration typically produced rapid changes in efflux of unlabelled sugar and steady-state-labelled l4 C-photosynthate. Osmoticum-induced changes in photosynthate efflux were caused by phloem import stimulation at low cell turgor and net efflux stimulation by high cell turgor. Even though rapid changes in sugar and tracer efflux were often induced by osmoticum treatments, the specific activity of sugar released from seed coats was not greatly affected by these treatments and was similar to the specific activity of sugar remaining in the seed coat after perfusion. Thus, tracer was transported from the phloem throughout the seed coat sugar pool before it was released to the apoplast. This result is most consistent with symplastic phloem unloading throughout perfused seed coats, because apoplastic transport between cells within the seed coat was blocked by perfusion. Photosynthate efflux was stimulated by simultaneous treatment of seed coats with EDTA and different concentrations of an osmoticum; loss of photosynthate from seed coats did not appear to be tissue-specific

P450 3A activity and cyclosporine dosing in kidney and heart transplant recipients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109917/1/cptclpt1994135.pd

Evaluation of intensive versus standard blood pressure reduction and association with cognitive decline and dementia : a systematic review and metaAnalysis

Importance: Optimal blood pressure (BP) targets for the prevention of cognitive impairment remain uncertain. Objective: To explore the association of intensive (i.e. lower than usual) BP reduction compared to guidelines on the incidence of cognitive decline and dementia in adults with hypertension. Data Sources and Study Selection: We conducted a systematic review and meta-analysis of randomized controlled trials that evaluated the association of intensive systolic BP lowering on cognitive outcomes by searching MEDLINE, Embase, CENTRAL, Web of Science, CINAHL, PsycINFO, ICTRP and ClinicalTrials.gov for data up to October 27, 2020. Data Extraction and Synthesis: Data screening and extraction were performed independently by two reviewers based on PRISMA guidelines. The risk of bias was assessed using the Cochrane risk-of-bias 2 tool. We used random-effects models using the inverse variance method for our pooled analyses. We evaluated the presence of potential heterogeneity with the I2 index. Main Outcomes and Measures: Our primary outcome was cognitive decline. Secondary outcomes included the incidence of dementia, mild cognitive impairment (MCI), cerebrovascular events, serious adverse events, and all-cause mortality. Results: From 7,755 citations, we identified sixteen publications from five trials (17,396 participants, mean age 65.7 years, 60.5% males) and two additional ongoing trials. All five trials included in quantitative analyses were considered at unclear to high risk of bias. The mean followup duration was 3.3 years (range 2.0 to 4.7 years). Intensive BP reduction was not significantly associated with global cognitive performance (SMD 0.01, 95% CI -0.04 to 0.06, I2 = 0%, four trials, 5,246 patients), incidence of dementia (RR 1.09, 95% CI 0.32 to 3.67, I2 = 27%, two trials, 9,444 patients) or incidence of MCI (RR 0.91, 95% CI 0.73 to 1.14, I2 = 74%, two trials, 10,774 patients) when compared to standard treatment. However, we found a reduction of cerebrovascular events in the intensive arm (RR 0.79, 95% CI 0.67-0.93, I2 = 0%, five trials, 17,396 patients) without an increased risk of serious adverse events or mortality. Conclusions and Relevance: We did not detect a significant association between BP reduction and lower risk of cognitive decline, dementia or MCI. The certainty of this evidence is low due to the limited sample size, the risk of bias of included trials and the observed statistical heterogeneity. Hence, current available evidence does not justify the use of lower BP targets for the prevention of cognitive decline and dementi

A mixed‐methods analysis of younger adults\u27 perceptions of asthma, self‐management, and preventive care: This isn\u27t helping me none

Background: Young adults (ages 18‐44) have increased emergency department use for asthma and poor adherence to medications. The objective of this mixed‐methods study was to understand experiences with and approaches to managing asthma, of which little is known in this age group. Methods: Surveys (Asthma Control Questionnaire, Asthma Quality of Life Questionnaire) and 1:1 semi‐structured interviews were used to explore experiences with asthma, symptoms, self‐management behaviors, and relationship to asthma control and quality of life. Qualitative data were analyzed using content analysis techniques. Descriptive statistics and bivariate correlations were used to examine distributive characteristics and associations between variables. Results: Forty urban adults participated (mean age 32.7 ± 6.2, 1σ). Coughing was reported nearly 46% more often than wheezing, with 42.5% (17/40) coughing until the point of vomiting most days. Most participants delayed using medication for symptoms due to misperceptions about inhalers. Higher symptom frequency and worse asthma control were associated with greater use of non‐pharmacologic symptom management strategies (r=0.645, p\u3c0.001; r=0.360, p=0.022, respectively). Five themes were identified regarding young adults experiences with asthma: (1) having asthma means being limited and missing out on life; (2) healthcare for asthma is burdensome and other things are more important; (3) there is not enough personal benefit in medical interactions to make preventive care worthwhile; (4) there is insufficient support and education about asthma for adults; and (5) people normalize chronic symptoms over time and find ways of coping that fit with their lifestyle. Conclusions & Clinical Relevance: Young adults may tolerate symptoms without using quick‐relief medication or seeking preventive care. Increasing engagement with preventive services will require decreasing perceived burdens and increasing the personal benefits of care. Evaluating for non‐pharmacologic approaches to managing symptoms and asthma‐related coughing may identify uncontrolled asthma. Enhanced training for clinicians in patient‐centric asthma care may be needed

Role of intestinal P‐glycoprotein ( mdr1 ) in interpatient variation in the oral bioavailability of cyclosporine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110064/1/cptclpt1997116.pd

Going Mobile with Primary Care: Smartphone-Telemedicine for Asthma Management in Young Urban Adults (TEAMS)

Background: The majority of adults with persistent asthma have chronically uncontrolled disease and interventions to improve outcomes are needed. We evaluated the efficacy, feasi- bility, and acceptability of a multi-component smartphone-telemedicine program (TEAMS) to deliver asthma care remotely, support provider adherence to asthma management guide- lines, and improve patient outcomes. Methods: TEAMS utilized: (1) remote symptom monitoring, (2) nurse-led smartphone-tele- medicine with self-management training for patients, and (3) Electronic medical record- based clinical decision support software. Adults aged 18-44 (N=33) and primary care providers (N=4) were recruited from a safety-net practice in Upstate New York. Asthma con- trol, quality of life, and FEV1 were measured at 0, 3 and 6 months. Acceptability was assessed via survey and end-of-study interviews. Paired t-test and mixed effects modeling were used to evaluate the effect of the intervention on asthma outcomes. Results: At baseline, 80% of participants had uncontrolled asthma. By 6-months, 80% classi- fied as well-controlled. Improvements in control and quality of life were large (d=1.955, d=1.579). FEV%pred increased 4.2% (d=1.687) with the greatest gain in males, smokers, and lower educational status. Provider adherence to national guidelines increased from 43.3% to 86.7% (CI = 22.11-64.55) and patient adherence to medication increased from 45.58% to 85.29% (CI = 14.79-64.62). Acceptability was 95.7%; In follow up interviews, 29/30 patients and all providers indicated TEAMS worked better than usual care, supported effective self- management, and reduced symptoms over time, which led to greater self-efficacy and motivation to manage asthma. Discussion: Based on these findings, we conclude that smartphone telemedicine could substantially improve clinical asthma management, adherence to guidelines, and patient outcomes

Understanding the threats posed by non-native species: public vs. conservation managers.

Public perception is a key factor influencing current conservation policy. Therefore, it is important to determine the influence of the public, end-users and scientists on the prioritisation of conservation issues and the direct implications for policy makers. Here, we assessed public attitudes and the perception of conservation managers to five non-native species in the UK, with these supplemented by those of an ecosystem user, freshwater anglers. We found that threat perception was not influenced by the volume of scientific research or by the actual threats posed by the specific non-native species. Media interest also reflected public perception and vice versa. Anglers were most concerned with perceived threats to their recreational activities but their concerns did not correspond to the greatest demonstrated ecological threat. The perception of conservation managers was an amalgamation of public and angler opinions but was mismatched to quantified ecological risks of the species. As this suggests that invasive species management in the UK is vulnerable to a knowledge gap, researchers must consider the intrinsic characteristics of their study species to determine whether raising public perception will be effective. The case study of the topmouth gudgeon Pseudorasbora parva reveals that media pressure and political debate has greater capacity to ignite policy changes and impact studies on non-native species than scientific evidence alone