Ten‐year attrition and antiretroviral therapy response among HIV‐positive adults: a sex‐based cohort analysis from eight West African countries

IntroductionSex differences have already been reported in sub‐Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow‐up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults.MethodsWe used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no‐follow‐up and 10‐year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively.ResultsA total of 71,283 patients (65.8% women) contributed to 310,007 person‐years of follow‐up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10‐year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow‐up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10‐year attrition throughout the 10‐year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/μL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/μL in their sixth year of follow‐up, whereas men failed to reach it even at the end of the 10‐year follow‐up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%).ConclusionsIn West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex‐adapted are needed for patients in care to monitor attrition, detect early high‐risk groups so that they can stay in care with a durably controlled infection.     

Development of a FRET-based fluorescence aptasensor for the detection of aflatoxin B1 in contaminated food grain samples

The present study aimed to develop an aptamer-based FRET detection strategy for the specific and sensitive detection of AFB1 in contaminated food grains. The study comprises generation of ssDNA aptamers against AFB1 by whole-cell SELEX and their application in a FRET-based platform utilizing graphene oxide (GO) and quantum dots (QDs). The generated aptamers were characterized to determine their specificity and sensitivity using indirect ELISA where AFB1–OVA was used as a coating antigen. Among the aptamers generated, the ATB1 aptamer showed good reactivity and selectivity against AFB1. This aptamer was further characterized to determine its secondary structure and KD value, which was found to be 5.9 kcal mol⁻¹. The characterized aptamers were conjugated onto Cd/Se quantum dots to develop a fluorimetric system for the detection of aflatoxin B1 using a graphene oxide platform. The presence of graphene oxide quenches the fluorescence ability of the quantum dots due to π–π stacking interactions between the aptamer and GO. Upon target addition, the aptamer forms a complex with aflatoxin B1 thereby restoring the fluorescence intensity. The developed assay shows a linear response from 0.002 μg μl⁻¹ to 0.2 μg μl⁻¹ with a detection limit of 0.004 μg μl⁻¹ for the AFB1 standard toxin and showed no cross-reactivity with other closely related mycotoxins. To validate the reliability of the developed method, several field samples spiked with AFB1 were included in this study and the results obtained were cross verified using a standard commercial AFB1 kit. In conclusion, the developed method may find good utility in routine food testing laboratories for risk assessment of AFB1.

The present study aimed to develop an aptamer-based FRET detection strategy for the specific and sensitive detection of AFB1 in contaminated food grains.     

Parental origin of mutation and the risk of breast cancer in a prospective study of women with a BRCA1 or BRCA2 mutation

The objective is to estimate the risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation, according to parental origin of mutation. We conducted a cohort study of women with a BRCA1 mutation (n = 1523) or BRCA2 mutation (n = 369) who had not been diagnosed with breast or ovarian cancer. For each woman, the pedigree was reviewed and the origin of the mutation was assigned as probable paternal or maternal. The hazard ratio (HR) for developing breast cancer in the follow‐up period was estimated for women with a paternal mutation compared to a maternal mutation. The risk of breast cancer was modestly higher in women with a paternal BRCA1 mutation compared to women with a maternal BRCA1 mutation (HR = 1.46; 95% CI = 0.99–2.16) but the difference was not significant (p = 0.06). The parental mutation origin did not affect the risk in women with a BRCA2 mutation. Our results are consistent with the hypothesis that there is an increased risk of breast cancer among women with a paternally inherited BRCA1 mutation compared to a maternally inherited mutation. However, the data are not sufficiently compelling to justify different screening recommendations for the two subgroups.     

Aging and probabilistic learning in single- and multiple-cue tasks

The objective of the study was to examine some of the conditions under which elderly people are able to learn probabilistic inverse relationships and when this type of learning is no longer possible. Two kind of tasks were used: (a) two single-cue learning tasks with either direct or inverse relationships (the Single-Cue Probability Learning paradigm), and (b) three two-cue learning tasks, one with two direct relationships, one with a combination of direct and inverse relationships, and one with two inverse relationships (the Multiple-Cue Probability Learning paradigm). Four groups of participants were included in the study: young adults (18- to 25-year-olds), adults (40- to 50-year-olds), elderly people (65- to 74-year-olds), and very elderly people (75- to 90-year-olds). It was shown that (a) older adults are able to reject the direct relationship "default" hypothesis and select the inverse relationship hypothesis when outcome feedback contradicting the default hypothesis is given, and provided that the learning setting be a very simple one, involving only one cue; (b) some older adults are able to select the inverse relationship hypothesis provided that the learning setting be a simple one,involving only two inverse relationship cues; and (c) very few older adults are able to select the inverse relationship hypothesis when the learning setting is a complex one, involving two cues with both direct and inverse relationships with the criterion. These results led to the revision of the "gradual decrease of cognitive flexibility in older adults" hypothesis proposed by Chasseigne, Mullet, and Stewart (Acta Psychologicgrave;a, 103, 229-238, 1997).     

Serodiagnosis of Schistosoma mansoni infections in an endemic area of Burkina Faso: performance of several immunological tests with different parasite antigens

The performance of indirect haemagglutination assays (IHA), enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescent antibody tests (IFAT) were compared with 450 sera from a Schistosoma mansoni-endemic area in Burkina Faso. All participants in this survey provided at least one sample each of stool, urine and serum. From those with an egg-negative Kato-Katz thick smear, a second stool sample was examined. IHA was based on either extracts of adult S. mansoni worms (SmIHA) or S. japonicum egg antigen (SjIHA). For ELISA, three antigen preparations were used, namely: (i) soluble S. mansoni adult worm antigens (SWAP); (ii) soluble S. mansoni egg antigens (SEA); and (iii) a cationic exchange fraction of S. mansoni eggs (CEF6). IFAT was performed with S. mansoni male worm sections. Among the egg-excretors, the sensitivity of ELISA was high and egg antigens performed slightly better (SEA, 96%; CEF6, 97%) than worm antigen (94%). Sensitivity of IHA was satisfactory with homologous (Sm, >85%), but not heterologous (Sj, 56%) parasite antigen. In IFAT, the parenchyma-associated fluorescence showed high sensitivity (95%), but gut-associated fluorescence, which is known to be a sensitive diagnostic marker for schistosome-infected European travelers, was observed only in 76% of a sub-sample of 100 of the endemic sera. Among sera from egg-negative individuals, many gave positive reactions in several or all of the tests employed. These reactions (formally "false positive") are considered to represent true infections, since chemotherapy had not yet been delivered to this population. For the purpose of further surveys in Burkina Faso or other resource-poor settings, we suggest IHA as an accurate diagnostic test and propose to further improve its performance by including egg rather than worm antigens.     

Orthostatic hypotension and cognitive impairment: a dangerous association?

Many studies have addressed the relation between orthostatic hypotension (OH) and cognitive impairment (CI) in the elderly, in mild cognitive impairment, vascular and neurodegenerative dementias and movement disorders, such as Parkinson’s disease. However, results concerning both the increased coexistence of the two conditions and their causal relationship remain controversial. According to the literature three hypotheses can be formulated on the relation between OH and CI. In neurodegenerative disease, OH and CI may result from a common pathological process which affects areas involved in both cognition and cardiovascular autonomic control. Alternatively, OH may lead to cerebral hypoperfusion which is supposed to play a role in the development of CI. Finally, recent data suggest that CI should probably be considered more a transient symptom of OH than a chronic effect. This study reviews the literature reports on the relationship between OH and CI, and emphasises the need for longitudinal studies designed to investigate this topic.     

Greffage d'acides aminés possédant une troisième fonction sur un polymère, 1. Fixation de tyrosine en extrémités de chaine. Modèle de réaction

The fixation of tyrosine through its phenolic function on α,ω-difunctional molecules was studied. Two methods were used: the first one consists in fixing a molecule of tyrosine on each terminating group of a diisocyanate with carbamate function; the second requires the preparation of a dimer of the tyrosine allowing the formation of a polymer through the condensation on the α,ω-bifunctional molecule.