CD4 dynamics over a 15 year-period among HIV controllers enrolled in the ANRS French observatory

Background

There are few large published studies of HIV controllers with long-term undetectable viral load (VL). We describe the characteristics and outcomes of 81 French HIV controllers.

Methods and Results

HIV controllers were defined as asymptomatic, antiretroviral-naïve persons infected ≥10 years previously, with HIV-RNA <400 copies/mL in >90% of plasma samples. All available CD4 and VL values were collected at enrolment. Mixed-effect linear models were used to analyze CD4 cell count slopes since diagnosis. HIV controllers represented 0.31% of all patients managed in French hospitals. Patients infected through intravenous drug use were overrepresented (31%) and homosexual men were underrepresented (26% of men) relative to the ANRS SEROCO cohort of subjects diagnosed during the same period. HIV controllers whose VL values were always below the detection limit of the assays were compared with those who had rare “blips” (<50% of VL values above the detection limit) or frequent blips (>50% of VL values above the detection limit). Estimated CD4 cell counts at HIV diagnosis were similar in the three groups. CD4 cell counts remained stable after HIV diagnosis in the “no blip” group, while they fell significantly in the two other groups (−0.26√CD4 and −0.28√CD4/mm³/year in the rare and frequent blip groups, respectively). No clinical, immunological or virological progression was observed in the no blip group, while 3 immunological and/or virological events and 4 cancers were observed in the blip subgroups.

Conclusions

Viral blips in HIV controllers are associated with a significant decline in CD4 T cells and may be associated with an increased risk of pathological events, possibly owing to chronic inflammation/immune activation.     

Visualization of elusive structures using intracardiac echocardiography: Insights from electrophysiology

Echocardiography has the ability to noninvasively explore hemodynamic variables during pharmacologic or exercise stress test in patients with heart failure. In this review, we detail some important potential applications of stress echocardiography in patients with heart failure. In patients with coronary artery disease and chronic LV dysfunction, dobutamine stress echocardiography is able to distinguish between viable and fibrotic tissue to make adequate clinical decisions. Exercise testing, in combination with echocardiographic monitoring, is a method of obtaining accurate information in the assessment of functional capacity and prognosis. Functional mitral regurgitation is a common finding in patients with dilated and ischaemic cardiomyopathy and stress echocardiography in the form of exercise or pharmacologic protocols can be useful to evaluate the behaviour of mitral regurgitation. It is clinical useful to search the presence of contractile reserve in non ischemic dilated cardiomyopathy such as to screen or monitor the presence of latent myocardial dysfunction in patients who had exposure to cardiotoxic agents. Moreover, in patients with suspected diastolic heart failure and normal systolic function, exercise echocardiography could be able to demonstrate the existence of such dysfunction and determine that it is sufficient to limit exercise tolerance. Finally, in the aortic stenosis dobutamine echocardiography can distinguish severe from non-severe stenosis in patients with low transvalvular gradients and depressed left ventricular function.     

Evaluating the evidence for targeting FOXO3a in breast cancer: a systematic review

Background

Tumour cells show greater dependency on glycolysis so providing a sufficient and rapid energy supply for fast growth. In many breast cancers, estrogen, progesterone and epidermal growth factor receptor-positive cells proliferate in response to growth factors and growth factor antagonists are a mainstay of treatment. However, triple negative breast cancer (TNBC) cells lack receptor expression, are frequently more aggressive and are resistant to growth factor inhibition. Downstream of growth factor receptors, signal transduction proceeds via phosphatidylinositol 3-kinase (PI3k), Akt and FOXO3a inhibition, the latter being partly responsible for coordinated increases in glycolysis and apoptosis resistance. FOXO3a may be an attractive therapeutic target for TNBC. Therefore we have undertaken a systematic review of FOXO3a as a target for breast cancer therapeutics.

Methods

Articles from NCBI were retrieved systematically when reporting primary data about FOXO3a expression in breast cancer cells after cytotoxic drug treatment.

Results

Increased FOXO3a expression is common following cytotoxic drug treatment and is associated with apoptosis and cell cycle arrest. There is some evidence that metabolic enzyme expression is also altered and that this effect is also elicited in TNBC cells. FOXO3a expression serves as a positive prognostic marker, especially in estrogen (ER) receptor positive cells.

Discussion

FOXO3a is upregulated by a number of receptor-dependent and -independent anti-cancer drugs and associates with apoptosis. The identification of microRNA that regulate FOXO3a directly suggest that it offers a tangible therapeutic target that merits wider evaluation.     

The dilemma of female mate selection in the brown bear, a species with sexually selected infanticide

Because of differential investment in gametes between sexes, females tend to be the more selective sex. Based on this concept, we investigate mate selection in a large carnivore: the brown bear (Ursus arctos). We hypothesize that, in this species with sexually selected infanticide (SSI), females may be faced with a dilemma: either select a high-quality partner based on phenotypic criteria, as suggested by theories of mate choice, or rather mate with future potentially infanticidal males as a counter-strategy to SSI. We evaluated which male characteristics were important in paternity assignment. Among males available in the vicinity of the females, the largest, most heterozygous and less inbred and also the geographically closest males were more often the fathers of the female's next litter. We suggest that female brown bears may select the closest males as a counter-strategy to infanticide and exercise a post-copulatory cryptic choice, based on physical attributes, such as a large body size, reflecting male genetic quality. However, male-male competition either in the form of fighting before copulation or during the post-copulatory phase, in the form of sperm competition, cannot entirely be ruled out.     

Biodiversity and ecology of epilithic diatoms in the Agnéby River,Ivory Coast

The ecology and taxonomy of the epilithic diatom flora of the Agnéby River, Ivory Coast were studied in 2012. Ten sites were investigated and diatoms were sampled on glass slides immersed for a period of 30 days during the wet and dry seasons. Physico-chemical parameters were measured at each site while sampling diatoms. Five taxa were largely dominant: Planothidium comperei CE Wetzel, N’Guessan and Tison-Rosebery, Eolimna minima (Grunow) Lange-Bertalot, Planothidium piaficum (JR Carter and Denny) CE Wetzel and Ector, Cocconeis schroederi Foged and Cocconeis scutellum var. parva (Grunow in Van Heurck) Cleve. Electrical conductivity, temperature, dissolved oxygen, nitrite and phosphorus were found to influence the distribution of taxa.     

The dynamic evolutionary history of the bananaquit (<Emphasis Type="Italic">Coereba flaveola</Emphasis>) in the Caribbean revealed by a multigene analysis

Background  

The bananaquit (Coereba flaveola) is a small nectivorous and frugivorous emberizine bird (order Passeriformes) that is an abundant resident throughout the Caribbean region. We used multi-gene analyses to investigate the evolutionary history of this species throughout its distribution in the West Indies and in South and Middle America. We sequenced six mitochondrial genes (3744 base pairs) and three nuclear genes (2049 base pairs) for forty-four bananaquits and three outgroup species. We infer the ancestral area of the present-day bananaquit populations, report on the species' phylogenetic, biogeographic and evolutionary history, and propose scenarios for its diversification and range expansion.     

New perspectives in diet analysis based on DNA barcoding and parallel pyrosequencing: the trnL approach

The development of DNA barcoding (species identification using a standardized DNA sequence), and the availability of recent DNA sequencing techniques offer new possibilities in diet analysis. DNA fragments shorter than 100-150 bp remain in a much higher proportion in degraded DNA samples and can be recovered from faeces. As a consequence, by using universal primers that amplify a very short but informative DNA fragment, it is possible to reliably identify the plant taxon that has been eaten. According to our experience and using this identification system, about 50% of the taxa can be identified to species using the trnL approach, that is, using the P6 loop of the chloroplast trnL (UAA) intron. We demonstrated that this new method is fast, simple to implement, and very robust. It can be applied for diet analyses of a wide range of phytophagous species at large scales. We also demonstrated that our approach is efficient for mammals, birds, insects and molluscs. This method opens new perspectives in ecology, not only by allowing large-scale studies on diet, but also by enhancing studies on resource partitioning among competing species, and describing food webs in ecosystems.     

Genetic estimates of annual reproductive success in male brown bears: the effects of body size, age, internal relatedness and population density

1. We studied male yearly reproductive success (YRS) and its determinants (phenotypic characteristics, age, population density) in two Scandinavian brown bear populations, using molecular techniques to determine paternity. 2. We found a significant difference in male YRS between the study areas, with lower YRS in the south than in the north. 3. In general, older and larger males had higher YRS. Older males may be more experienced in competition for reproduction (male dominance). Large body size is of direct benefit in male-male competition and of advantage in endurance competition for the access to females. 4. Age was relatively more important for YRS in the north and body size was more important in the south, due perhaps to differences in male age structure due to illegal killing. A single old male dominated the reproduction in the north during the study, which resulted most probably in the relatively higher importance of age in the north. In the south, with a more even male age structure, no single male was able to dominate, probably resulting in a more intense competition among males, with body size as the deciding factor. 5. Male YRS was correlated positively with population density. This may be related to the structure of the expanding bear population, with female densities declining towards the population edge. 6. Internal relatedness, a measure of genetic heterozygosity, was correlated negatively with YRS, suggesting that outbred individuals have a higher YRS. Individual heterozygosity at key or many loci may reflect male physical qualities and condition-sensitive traits, which may benefit males directly in contest or in sperm competition.