Association between a Specific Pneumocystis jiroveci Dihydropteroate Synthase Mutation and Failure of Pyrimethamine/Sulfadoxine Prophylaxis in Human Immunodeficiency Virus-Positive and -Negative Patients

To investigate the possible association between different prophylactic sulfa drugs and the genotype of the Pneumocystis jiroveci dihydropteroate synthase (DHPS) gene, we examined DHPS polymorphisms in clinical specimens from 158 immunosuppressed patients (38 HIV-negative and 120 HIV-positive), using polymerase chain reaction-single-strand conformation polymorphism. Fifty-seven (36.1%) of 158 patients were infected with a mutant DHPS genotype. All patients who developed P. jiroveci pneumonia (PcP) while receiving pyrimethamine/sulfadoxine (PM/SD) prophylaxis (n=14) had a strain harboring DHPS with an amino acid change at position 57 (Pro→Ser). This mutation was only present in 20 (14%) of 144 patients not receiving prophylaxis (P<.001). Hospitalization in a specific hospital was an independent risk factor for having P. jiroveci harboring the same DHPS mutation, which indirectly supports that interhuman transmission may affect the dissemination of the mutant strain

Human amniotic membranes as an allogenic biological dressing for the treatment of burn wounds: Protocol for a randomized-controlled study

Background: Burn wounds pose significant challenges in medical treatment due to their devastating nature and resource-intensive requirements. Temporary coverage of burn wounds using synthetic or biological dressings allows for reepithelization before definitive skin grafting. Allogenic skin grafts have been widely used but come with drawbacks such as rejection and disease transmission. The use of amniotic membranes (AMs) offers a promising alternative for temporary coverage, as they possess biological properties that promote faster healing and improved scar quality. The various components of the amniotic membrane, including pluripotent stem cells, extracellular matrix proteins, and regenerative factors, contribute to cell growth, migration, and differentiation, as well as preservation of the original epithelial phenotype. Objective: Reliable information on the treatment of burn wounds with AM is needed. The knowledge gained in this project may help to include this advantageous modern concept of biological dressings in clinical practice. The purpose of this study is to use human amniotic membranes from our in hospital laboratory, as an allogenic biological dressing after enzymatic debridement in superficial partial thickness, deep partial thickness or full thickness burn wounds. Methods: We will include 30 patients in a randomized-controlled trial with each patient receiving the study intervention and the control intervention. Two 7 × 7 cm burn wound areas will be compared regarding per centage of skin graft take, healing time, healing percentage value and total healing time. Human amniotic membranes will be compared to allogenic skin grafts

Impaired ABCA1/ABCG1-mediated lipid efflux in the mouse retinal pigment epithelium (RPE) leads to retinal degeneration

Age-related macular degeneration (AMD) is a progressive disease of the retinal pigment epithelium (RPE) and the retina leading to loss of central vision. Polymorphisms in genes involved in lipid metabolism, including the ATP-binding cassette transporter A1 (), have been associated with AMD risk. However, the significance of retinal lipid handling for AMD pathogenesis remains elusive. Here, we study the contribution of lipid efflux in the RPE by generating a mouse model lacking ABCA1 and its partner ABCG1 specifically in this layer. Mutant mice show lipid accumulation in the RPE, reduced RPE and retinal function, retinal inflammation and RPE/photoreceptor degeneration. Data from human cell lines indicate that the AMD risk-conferring allele decreases expression, identifying the potential molecular cause that underlies the genetic risk for AMD. Our results highlight the essential homeostatic role for lipid efflux in the RPE and suggest a pathogenic contribution of reduced ABCA1 function to AMD

Hif1a inactivation rescues photoreceptor degeneration induced by a chronic hypoxia-like stress

Reduced choroidal blood flow and tissue changes in the ageing human eye impair oxygen delivery to photoreceptors and the retinal pigment epithelium. As a consequence, mild but chronic hypoxia may develop and disturb cell metabolism, function and ultimately survival, potentially contributing to retinal pathologies such as age-related macular degeneration (AMD). Here, we show that several hypoxia-inducible genes were expressed at higher levels in the aged human retina suggesting increased activity of hypoxia-inducible transcription factors (HIFs) during the physiological ageing process. To model chronically elevated HIF activity and investigate ensuing consequences for photoreceptors, we generated mice lacking von Hippel Lindau (VHL) protein in rods. This activated HIF transcription factors and led to a slowly progressing retinal degeneration in the ageing mouse retina. Importantly, this process depended mainly on HIF1 with only a minor contribution of HIF2. A gene therapy approach using AAV-mediated RNA interference through an anti-Hif1a shRNA significantly mitigated the degeneration suggesting a potential intervention strategy that may be applicable to human patients

Characterization of bamboo foam films by neutron and X-ray experiments

International audienceWe report on small angle neutron and X-ray scattering experiments on single common black films in ordered bamboo foams stabilized by sodium dodecyl sulfate and dodecanol. We observed anisotropic scattering perpendicular to the film. The integrated signal exhibits clear Kiessig fringes over a wide range of diffusion vector q. We were able to fit our data by a single layer (neutron with contrast matching water/SDS) or a "three slabs" (X-ray) reflectivity. We also discuss about the wide range of reflected angle, despite the narrow distribution of incident angles. Though thermal surface fluctuations may induce off-specular reflectivity, we show here a simple geometrical explanation of the phenomenon. This angle distribution is indeed compatible with the curvature of the film

Sulfa resistance and dihydropteroate synthase mutants in recurrent Pneumocystis carinii pneumonia.

Failure of sulfa or sulfone prophylaxis is associated with mutations in Pneumocystis carinii gene coding for dihydropteroate synthase (DHPS). The DHPS genotype was analyzed in AIDS patients who had two separate episodes of P. carinii pneumonia. The results suggest that DHPS mutations can be selected de novo within patients by the pressure of a sulfa or sulfone drug

In-situ SAXS Study of Aqueous Clay Suspensions Submitted to Alternating Current Electric Fields

International audienc