[Is ovarian function impaired in HIV patients? A clinical pilot study in Burkina Faso]. / La fonction ovarienne est-elle altérée chez les patientes séropositives pour le VIH? Une étude pilote au Burkina Faso.

A lot of studies published on the ten last years showed a decrease of fertility among HIV positive women. The present research aims to see if this decrease is linked to an ovarian failure, using AMH as principal marker of ovarian function. In this pilot study, 54 HIV-positive and 39 HIV-negative women were compared on the basis of their ovarian function, fecundity and possible ovarian failure. A blood sample was taken for hormonal titrations, HIV seropositivity, viral load and CD4 T cell count. An interview explored demographic characteristics, obstetrical and infectious history, and menstrual characteristics. This study was performed in Burkina Faso between January and February 2008. There is no significant difference after adjusting for age of AMH level between the two groups. However, in our study, 5.5% of HIV positive women had a premature menopause, which is a significant variation from the premature menopause rates of the African population, which is 1.4%. In conclusion, this study put the HIV impact on ovarian function into perspective but the high premature menopause rates could suggest an ovarian attack by the virus or the treatment.

Glucose-Dependent Insulin Secretion from ß Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide.

Type 1 diabetes results from the loss of pancreatic ß cells, reduced insulin secretion and dysregulated blood glucose levels. Replacement of these lost ß cells with stem cell-derived ß cells, and protecting these cells within macro-device implants is a promising approach to restore glucose homeostasis. However, to achieve this goal of restoration of glucose balance requires work to optimise ß cell function within implants. We know that native ß cell function is enhanced by cell-cell and cell-extracellular matrix interactions within the islets of Langerhans. Reproducing these interactions in 2D, such as culture on matrix proteins, does enhance insulin secretion. However, the impact of matrix proteins on the 3D organoids that would be in implants has not been widely studied. Here, we use native ß cells that are dispersed from islets and reaggregated into small spheroids. We show these ß cell spheroids have enhanced glucose-dependent insulin secretion when embedded into softer alginate hydrogels conjugated with RGD peptide (a common motif in extracellular matrix proteins). Embedding into alginate-RGD causes activation of integrin responses and repositioning of liprin, a protein that controls insulin secretion. We conclude that insulin secretion from ß cell spheroids can be enhanced through manipulation of the surrounding environment.

In Situ Coatings of Silver Nanoparticles for Biofilm Treatment in Implant-Retention Surgeries: Antimicrobial Activities in Monoculture and Coculture.

Bacterial biofilms are indicated in most medical device-associated infections. Treating these biofilms is challenging yet critically important for applications such as in device-retention surgeries, which can have reinfection rates of up to 80%. This in vitro study centered around our new method of treating biofilm and preventing reinfection. Ionic silver (Ag, in the form of silver nitrate) combined with dopamine and a biofilm-lysing enzyme (α-amylase) were applied to model 4-day-old Staphylococcus aureus biofilms on titanium substrates to degrade the extracellular matrix of the biofilm and kill the biofilm bacteria. In this process, the oxidative self-polymerization of dopamine converted Ag ions into Ag nanoparticles that, together with the resultant self-adhering polydopamine (PDA), formed coatings that strongly bound to the treated substrates. Surprisingly, although these Ag/PDA coatings significantly reduced S. aureus growth in standard bacterial monoculture, they showed much lower antimicrobial activity in coculture of the bacteria and osteoblastic MC3T3-E1 cells in which the bacteria were also found attached to the osteoblasts. This S. aureus- osteoblast interaction was also linked to bacterial survival against gentamicin treatment observed in coculture. Our study thus provided clear evidence suggesting that bacteria's interactions with tissue cells surrounding implants may significantly contribute to their resistance to antimicrobial treatment.

Towards engineering heart tissues from bioprinted cardiac spheroids.

Currentin vivoandin vitromodels fail to accurately recapitulate the human heart microenvironment for biomedical applications. This study explores the use of cardiac spheroids (CSs) to biofabricate advancedin vitromodels of the human heart. CSs were created from human cardiac myocytes, fibroblasts and endothelial cells (ECs), mixed within optimal alginate/gelatin hydrogels and then bioprinted on a microelectrode plate for drug testing. Bioprinted CSs maintained their structure and viability for at least 30 d after printing. Vascular endothelial growth factor (VEGF) promoted EC branching from CSs within hydrogels. Alginate/gelatin-based hydrogels enabled spheroids fusion, which was further facilitated by addition of VEGF. Bioprinted CSs contracted spontaneously and under stimulation, allowing to record contractile and electrical signals on the microelectrode plates for industrial applications. Taken together, our findings indicate that bioprinted CSs can be used to biofabricate human heart tissues for long termin vitrotesting. This has the potential to be used to study biochemical, physiological and pharmacological features of human heart tissue.

Polydopamine coating of uncrosslinked chitosan as an acellular scaffold for full thickness skin grafts.

There is an unmet need for skin grafting materials that are readily available for large area wounds, due to complex, lengthy and costly manufacturing processes that are not compatible with this type of wounds. Here we developed an acellular skin graft material based on surface coating of uncrosslinked porous (UCLP) chitosan. UCLP chitosan membranes had mechanical properties in ranges suitable for skin grafting. Polydopamine (PDA) coating improved hydrophilicity and resulted in a significant increase in attachment and metabolic activity of mammalian cells in vitro. PDA coating also decreased the attachment of pseudomonas aeruginosa - a common bacteria infecting skin wounds. Finally, the PDA-coated membranes were implanted in full thickness surgical wounds in a rodent model and resulted in complete would closure in 5 days. The current study suggests that PDA-coated UCLP chitosan membranes could be a simple and effective strategy for the development of grafting materials for large area wounds.

Immobilization-Enhanced Eradication of Bacterial Biofilms and in situ Antimicrobial Coating of Implant Material Surface - an in vitro Study.

PURPOSE: The aim of this study was to investigate a new method of in situ biofilm treatment for infected prostheses that remove bacterial biofilm and prevent reinfection through the use of an immobilizing agent in combination with the actions of biofilm-lysing enzymes and bactericidal antimicrobials. METHODS: We investigated the combination of self-immobilization chemistry of dopamine with a biofilm-lysing enzyme, α-amylase (Am), and an antimicrobial agent, silver nitrate (Ag), to treat model Staphylococcus aureus (S. aureus) biofilms formed on titanium. The efficacy of biofilm removal and bacterial treatment was analyzed by crystal violet, colony-forming unit assays, confocal laser scanning microscopy, and scanning electron microscopy (SEM). To confirm the in situ coating of the titanium surface with antimicrobial Ag as a strategy to prevent bacterial recolonization, SEM in secondary electron mode (SE), backscatter electron mode, (BSE) and energy-dispersive spectroscopy (EDX) were used. The antimicrobial activity of the coated surface was evaluated by optical density measurement and colony-forming unit assays. RESULTS: Polydopamine (PDA)-assisted treatment showed approximately a 2 log reduction in recoverable CFU and a 15% increase in biofilm removal efficacy compared to treatments that had only Am or Ag. More importantly, PDA-assisted treatment was found to immobilize Ag on the surface after the treatment, rendering them resistant to bacterial recolonization. CONCLUSION: Our in vitro findings suggested that this PDA-assisted treatment and the surface immobilization-enhanced treatment concept could be promising in the development of advanced treatment for implant retention surgery for an infected prosthesis.

Immobilization of Antimicrobial Silver and Antioxidant Flavonoid as a Coating for Wound Dressing Materials.

PURPOSE: The aim of this study is to develop a new coating for wound dressings that is comprised of antimicrobial silver (Ag) and antioxidant flavonoid quercetin (Q). METHODS: Dip-coating was used to apply the coating on cotton gauge as a model dressing. Ag was immobilised using polydopamine as a priming and catalytic layer followed by coating of quercetin that was incorporated in a functionalized polydimethylsiloxane. The coating was investigated using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) and release assay. The antimicrobial activity of quercetin and Ag was tested against Staphylococcus aureus (S. aureus). A surgical wound model on mice was used to evaluate the effects of the coated dressing on wound healing rates and tissue histology. RESULTS: Ag and quercetin showed enhanced antimicrobial activity against S. aureus when used in combination. Ag and quercetin were successfully immobilized onto the fibre of the dressing using the dip-coating process. The coating released Ag and quercetin over 8 days and showed strong antioxidant activity. In the wound healing model, complete wound closure was achieved in 12 days in the group receiving coated dressing and was associated with an enhancement in tissue remodelling and neo-angiogenesis and the reduction in tissue inflammation. CONCLUSION: These new antimicrobial-antioxidant coatings may be promising in the development of advanced wound care therapies.

Evaluation of the Pastorex meningitis kit for the rapid identification of Neisseria meningitidis serogroups A and W135.

The recent emergence of Neisseria meningitidis W135 as a cause of epidemic bacterial meningitis and the availability of a trivalent ACW135 vaccine have created a need for accurate and timely meningococcal serogroup determination for organization of epidemic vaccine response. The sensitivity and specificity of the Pastorex meningitis kit (Bio-Rad) to identify serogroups A and W135 in the African meningitis belt was assessed using PCR testing as the gold standard. The sensitivity and specificity for serogroups A and W135 were 87 and 85%, respectively, while the specificities were 93 and 97%. The positive and negative likelihood ratios for A were 12 and 0.14 and for W135 were 33 and 0.16. The positive and negative predictive values, computed to simulate an epidemic of meningococcal meningitis with an estimated 70% prevalence of N. meningitidis among suspected cases, were 97% and 75% for A and 99% and 73% for W135. In remote locations of the African meningitis belt, latex agglutination is the only currently available test that can rapidly determine meningococcal serogroup. This study showed that latex agglutination performs well and could be used during the epidemic season to determine appropriate vaccine response.

24-Month adherence, tolerance and efficacy of once-a-day antiretroviral therapy with didanosine, lamivudine, and efavirenz in African HIV-1 infected children: ANRS 12103/12167.

BACKGROUND: There is no data on long-term benefit of once-a-day antiretroviral therapy (ART) with combination of DDI, 3TC and EFV to allow its use in future therapeutic strategies. OBJECTIVES: To assess 24-month immuno-virological, adherence, tolerance, and effectiveness of a once-a-day ART with DDI, 3TC and EFV. METHODS: A phase 2 open trial including 51 children aged from 30 months to 15 years, monitored a once-a-day regimen for 24 months from 2006 to 2008 in the Departement de Pediatrie du CHUSS, at Bobo-Dioulasso in Burkina Faso. We tested immunological and virological response, adherence, tolerance and resistance of the treatment. RESULTS: Children with CD4 >25% at 24 months were 67.4% (33/49) CI 95% [54%, 80%]. The proportion of children with viral plasma RNA <300 cp / ml at 24 months of treatment was 81.6 % (40/49) CI [68.0% 91.2%]. Good adherence was obtained with more than 88% adherence > 95% over the 24 months. Drugs were well tolerated. CONCLUSIONS: Given the limited number of antiretroviral drugs available in Africa and the inadequacy of laboratory monitoring in support program, once-a-day treatment and especially the DDI-based combination strategies could be an attractive operational option.

Incidence of tuberculosis after HAART initiation in a cohort of HIV-positive patients in Burkina Faso.

OBJECTIVE: To determine the incidence rates of tuberculosis (TB) after the initiation of highly active antiretroviral treatment (HAART). METHODS: We conducted a retrospective cohort study on four human immunodeficiency virus (HIV) treatment centres in Ouagadougou, Burkina Faso. TB incidence was measured at different intervals after HAART initiation. Cox regression models were used to identify factors associated with TB incidence. RESULTS: We analysed a cohort of 2383 subjects with a mean follow-up period of 836 days (standard deviation +/- 443.4). TB incidence rate was highest during the first trimester of HAART; after 3 months of treatment, the total TB case incidence dropped by 60% from 5.77/100 person-years (py) to 2.23/100 py. World Health Organization clinical Stage III or IV, CD4+ T-cell count < 50 cells/microl and body mass index (BMI) < 18.5 were associated with increased risk of TB on univariate analysis. In the Cox regression, BMI < 18.5 and CD4+ T-cell count < 50 cells/microl at HAART initiation were independently associated with a two-fold higher risk of TB. CONCLUSIONS: Delaying HAART initiation until the CD4+ T-cell count drops to <50 cells/microl significantly increases TB incidence in the first 3 months after HAART initiation. Active case finding for TB is an essential element of standard clinical care in HIV-positive patients during the initial period of HAART.