A nodulo-cystic eumycetoma caused by Pyrenochaeta romeroi in a renal transplant recipient: A case report

<p>Abstract</p> <p>Introduction</p> <p><it>Pyrenochaeta romeroi </it>(<it>P. romeroi</it>) is a saprophytic fungus found in soil and plants. The fungal spores can be introduced into deeper tissues by trauma. It causes eumycetoma, which affects skin and subcutaneous tissues.</p> <p>Case presentation</p> <p>A 57-year-old South Asian man presented with a painless, nodular lesion (1 cm × 0.5 cm) on the left knee. He had had a renal transplant eight months earlier for end-stage renal failure. The patient was on tacrolimus, mycophenolate mofetil and prednisolone for immunosuppression. The lesion had progressed dramatically (to 5 cm × 5 cm) despite antibiotic treatment. The size and location of the lesion was severely affecting his quality of life, so an excision biopsy was performed. Nuclear ribosomal repeat-region sequencing confirmed the causative organism as <it>P. romeroi</it>. An <it>in vitro </it>antifungal susceptibility test demonstrated that <it>P. romeroi </it>was sensitive to voriconazole. Following a successful surgical removal, voriconazole was continued orally for two months.</p> <p>Conclusion</p> <p>To the best of our knowledge, we are reporting the first case of Eumycetoma caused by <it>P. romeroi </it>in a renal transplant recipient. Physicians should be aware of this rare fungal disease in transplant recipients. We recommend a combination of medical and surgical management in these immunosuppressed patients.</p

Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses

Phase 1 Trial of AMA1-C1/Alhydrogel plus CPG 7909: An Asexual Blood-Stage Vaccine for Plasmodium falciparum Malaria

Apical Membrane Antigen 1 (AMA1), a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909.A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 15), 80 microg of AMA1-C1/Alhydrogel (n = 30), or 80 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 30).Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG) were detected by enzyme-linked immunosorbent assay (ELISA), and the immune sera of volunteers that received 20 microg or 80 microg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 microg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition.The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing.ClinicalTrials.gov NCT00344539

Dengue Virus Infection of the Aedes aegypti Salivary Gland and Chemosensory Apparatus Induces Genes that Modulate Infection and Blood-Feeding Behavior

The female Aedes aegypti salivary gland plays a pivotal role in bloodmeal acquisition and reproduction, and thereby dengue virus (DENV) transmission. It produces numerous immune factors, as well as immune-modulatory, vasodilatory, and anti-coagulant molecules that facilitate blood-feeding. To assess the impact of DENV infection on salivary gland physiology and function, we performed a comparative genome-wide microarray analysis of the naïve and DENV infection-responsive A. aegypti salivary gland transcriptomes. DENV infection resulted in the regulation of 147 transcripts that represented a variety of functional classes, including several that are essential for virus transmission, such as immunity, blood-feeding, and host-seeking. RNAi-mediated gene silencing of three DENV infection-responsive genes - a cathepsin B, a putative cystatin, and a hypothetical ankyrin repeat-containing protein - significantly modulated DENV replication in the salivary gland. Furthermore, silencing of two DENV infection-responsive odorant-binding protein genes (OBPs) resulted in an overall compromise in blood acquisition from a single host by increasing the time for initiation of probing and the probing time before a successful bloodmeal. We also show that DENV established an extensive infection in the mosquito's main olfactory organs, the antennae, which resulted in changes of the transcript abundance of key host-seeking genes. DENV infection, however, did not significantly impact probing initiation or probing times in our laboratory infection system. Here we show for the first time that the mosquito salivary gland mounts responses to suppress DENV which, in turn, modulates the expression of chemosensory-related genes that regulate feeding behavior. These reciprocal interactions may have the potential to affect DENV transmission between humans

Morphometric, hemodynamic and biomechanical factors influencing blood flow and oxygen concentration in the human lamina cribrosa

Purpose : We developed a combined biomechanical and hemodynamic model of the human eye to estimate blood flow and oxygen concentration within the lamina cribrosa (LC), and rank the factors that influence LC oxygen concentration. Methods : We generated 4,000 finite element (FE) eye models with detailed LC microcapillary networks and computed the oxygen concentration within the axons at the level of the LC. We assumed that biomechanical loads (such as intraocular pressure [IOP] or cerebrospinal fluid pressure [CSFP]) could directly affect the 3D configurations and the lumen diameter of the LC microcapillary networks (Figure 1a-d), and thus influence hemodynamics and oxygen concentrations. For each model, we varied the IOP (38+-19 mmHg), the CSFP (19+-7 mmHg), cup-depth (0.2+-0.1 mm), scleral stiffness (+-20% of mean values), LC stiffness (0.41+-0.2 MPa), LC Radius (1.2+-0.1 mm), average LC pore size (5500+-2400 µm2) and the microcapillary arrangement (radial, isotropic or circumferential). Blood flow was assumed to originate from the LC periphery (arterial pressure: 50+-7 mmHg) and drainage occurred via the central retinal vein (venous pressure: 16+-5 mmHg). Finally, we performed linear regressions to rank the influence of each factor on the LC’s tissue oxygen concentration. Results : LC radius, arterial pressure and venous pressure were the most important factors influencing the oxygen concentration within the LC (Figure 1e). IOP was another important parameter and eyes with higher IOP had higher compressive strain and significantly lower oxygen concentration. On average, an increase in IOP of 40 mmHg resulted in a decrease in oxygen concentration of 2 mmHg. In general, supero-inferior regions of the LC had significantly lower oxygen concentration than naso-temporal regions, resulting in an hourglass pattern of oxygen distribution. Conclusions : This study presents a comprehensive hemodynamical model of the eye that accounts for the biomechanical forces and detailed morphological parameters of the LC. The results provide further insight into the possible relationship of biomechanical and vascular pathways leading to ischemia-induced optic neuropathy

Morphometric, hemodynamic and biomechanical factors influencing blood flow and oxygen concentration in the human lamina cribrosa

Purpose : We developed a combined biomechanical and hemodynamic model of the human eye to estimate blood flow and oxygen concentration within the lamina cribrosa (LC), and rank the factors that influence LC oxygen concentration. Methods : We generated 4,000 finite element (FE) eye models with detailed LC microcapillary networks and computed the oxygen concentration within the axons at the level of the LC. We assumed that biomechanical loads (such as intraocular pressure [IOP] or cerebrospinal fluid pressure [CSFP]) could directly affect the 3D configurations and the lumen diameter of the LC microcapillary networks (Figure 1a-d), and thus influence hemodynamics and oxygen concentrations. For each model, we varied the IOP (38+-19 mmHg), the CSFP (19+-7 mmHg), cup-depth (0.2+-0.1 mm), scleral stiffness (+-20% of mean values), LC stiffness (0.41+-0.2 MPa), LC Radius (1.2+-0.1 mm), average LC pore size (5500+-2400 µm2) and the microcapillary arrangement (radial, isotropic or circumferential). Blood flow was assumed to originate from the LC periphery (arterial pressure: 50+-7 mmHg) and drainage occurred via the central retinal vein (venous pressure: 16+-5 mmHg). Finally, we performed linear regressions to rank the influence of each factor on the LC’s tissue oxygen concentration. Results : LC radius, arterial pressure and venous pressure were the most important factors influencing the oxygen concentration within the LC (Figure 1e). IOP was another important parameter and eyes with higher IOP had higher compressive strain and significantly lower oxygen concentration. On average, an increase in IOP of 40 mmHg resulted in a decrease in oxygen concentration of 2 mmHg. In general, supero-inferior regions of the LC had significantly lower oxygen concentration than naso-temporal regions, resulting in an hourglass pattern of oxygen distribution. Conclusions : This study presents a comprehensive hemodynamical model of the eye that accounts for the biomechanical forces and detailed morphological parameters of the LC. The results provide further insight into the possible relationship of biomechanical and vascular pathways leading to ischemia-induced optic neuropathy

Bulk changes in posterior scleral collagen microstructure in human high myopia

MOLECULAR VISION24818-83