Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases.

Invasive fungal infections (IFI) of the Central Nervous System (IFI-CNS) and Paranasal Sinuses (IFI-PS) are rare, life-threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI-CNS (71/89) and IFI-PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5-79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI-CNS, and a sinus biopsy was performed in 56% of IFI-PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI-CNS (30/71), and it was positive in 67%. Eighty-four pts received a first-line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5-835). A surgical intervention was performed in 26% of cases but only 10% of IFI-CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1-year overall survival was 32% without significant differences between IFI-CNS and IFI-PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of newer antifungal drugs. The results arising from this large contemporary cohort of cases may allow a more effective diagnostic and therapeutic management of these very rare IFI complications in haematologic patients.

Impact of nutritional status on vaccine-induced immunity in children living in South Africa: Investigating the B-cell repertoire and metabolic hormones.

OBJECTIVES: We explored the role of metabolic hormones and the B-cell repertoire in the association between nutritional status and vaccine responses. METHODS: In this prospective cohort study, nested within a larger randomized open-label trial, 211 South African children received two doses of measles vaccine and two or three doses of pneumococcal conjugate vaccine (PCV). Metabolic markers (leptin, ghrelin and adiponectin) and distribution of B-cell subsets (n = 106) were assessed at 18 months of age. RESULTS: Children with a weight-for-height z-score (WHZ) ≤ -1 standard deviation (SD) at booster vaccination had a decreased mean serotype-specific PCV IgG response compared with those with WHZ > -1 and <+1 SD or WHZ ≥ +1 SD at 9 months post-booster (18 months of age). (Naive) pre-germinal center B-cells were associated with pneumococcal antibody decay between one to nine months post-booster. Predictive performance of elastic net models for the combined effect of B-cell subsets, metabolic hormones and nutritional status (in addition to age, sex, and randomization group) on measles and PCV vaccine response had an average area under the receiver operating curve of 0.9 and 0.7, respectively. CONCLUSIONS: The combined effect of B-cell subsets, metabolic hormones and nutritional status correlated well with the vaccination response for measles and most PCV serotypes. CLINICALTRIALS: gov registration of parent studies: NCT02943902 and NCT03330171.

Evaluation of indigenous bacterial strains for biocontrol of the frogeye leaf spot of soya bean caused by Cercospora sojina.

AIMS: Assessment of biological control of Cercospora sojina, causal agent of frogeye leaf spot (FLS) of soya bean, using three indigenous bacterial strains, BNM297 (Pseudomonas fluorescens), BNM340 and BNM122 (Bacillus amyloliquefaciens). METHODS AND RESULTS: From cultures of each bacterial strain, cell suspensions and cell-free supernatants were obtained and assayed to determine their antifungal activity against C. sojina. Both mycelial growth and spore germination in vitro were more strongly inhibited by bacterial cell suspensions than by cell-free supernatants. The Bacillus strains BNM122 and BNM340 inhibited the fungal growth to a similar degree (I ≈ 52-53%), while cells from P. fluorescens BNM297 caused a lesser reduction (I ≈ 32-34%) in the fungus colony diameter. The foliar application of the two Bacillus strains on soya bean seedlings, under greenhouse conditions, significantly reduced the disease severity with respect to control soya bean seedlings and those sprayed with BNM297. This last bacterial strain was not effective in controlling FLS in vivo. CONCLUSIONS: Our data demonstrate that the application of antagonistic bacteria may be a promising and environmentally friendly alternative to control the FLS of soya bean. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first report of biological control of C. sojina by using native Bacillus strains.

Two DHH subfamily 1 proteins contribute to pneumococcal virulence and confer protection against pneumococcal disease.

Streptococcus pneumoniae is an important human bacterial pathogen, causing such infections as pneumonia, meningitis, septicemia, and otitis media. Current capsular polysaccharide-based conjugate vaccines protect against a fraction of the over 90 serotypes known, whereas vaccines based on conserved pneumococcal proteins are considered promising broad-range alternatives. The pneumococcal genome encodes two conserved proteins of an as yet unknown function, SP1298 and SP2205, classified as DHH (Asp-His-His) subfamily 1 proteins. Here we examined their contribution to pneumococcal pathogenesis using single and double knockout mutants in three different strains: D39, TIGR4, and BHN100. Mutants lacking both SP1298 and SP2205 were severely impaired in adherence to human epithelial Detroit 562 cells. Importantly, the attenuated phenotypes were restored upon genetic complementation of the deleted genes. Single and mixed mouse models of colonization, otitis media, pneumonia, and bacteremia showed that bacterial loads in the nasopharynx, middle ears, lungs, and blood of mice infected with the mutants were significantly reduced from those of wild-type-infected mice, with an apparent additive effect upon deletion of both genes. Minor strain-specific phenotypes were observed, i.e., deletion of SP1298 affected host-cell adherence in BHN100 only, and deletion of SP2205 significantly attenuated virulence in lungs and blood in D39 and BHN100 but not TIGR4. Finally, subcutaneous vaccination with a combination of both DHH subfamily 1 proteins conferred protection to nasopharynx, lungs, and blood of mice infected with TIGR4. We conclude that SP1298 and SP2205 play a significant role at several stages of pneumococcal infection, and importantly, these proteins are potential candidates for a multicomponent protein vaccine.

Intraspecific variability of specific leaf area fosters the persistence of understorey specialists across a light availability gradient.

Forest understorey plants are sensitive to light availability, and different species groups can respond differently to changing light conditions. A plant trait tightly linked to light capture is specific leaf area (SLA). Studies considering the relative role of within- and among-species SLA variation across different species groups (e.g. specialists and generalists) are rarely implemented in temperate forest understories varying in their maturity. We examined community-level SLA patterns of beech forest understories along a light availability gradient, and for habitat specialists and generalists separately. We then disentangled and quantified the contribution of intraspecific trait variability and interspecific trait differences in shaping SLA patterns. We revealed that the increase in community-level SLA with decreasing light availability was primarily driven by beech forest specialists (and, to a lesser extent, by forest generalists), and this pattern was mainly determined by specialists' high intraspecific variability. Community-level SLA was therefore formed by different responses at different organizational levels, i.e. within and among species, and for separate species groups. This study provides insights into factors shaping the shade tolerance strategy in beech forest understorey plants; specialists persistence under putative less favourable conditions (i.e. high irradiation) may be fostered by their ability to adjust their light capture strategies intraspecifically.

Long-term olive oil-based parenteral nutrition sustains innate immune function in home patients without active underlying disease.

BACKGROUND & AIMS: It remains unclear whether impaired host defenses contribute to the increased risk for infectious complications seen in patients on home parenteral nutrition (HPN). The aim of this study was to compare the innate immune function of patients on olive oil-based HPN with that of healthy controls. METHODS: Innate immune functions and (anti-)oxidant balance were studied in 20 patients on olive oil-based HPN without an active underlying immune-mediated disease (Clinoleic(®), ≥ 6 months; >3 times/week), and 21 age- and sex-matched healthy controls. RESULTS: Neutrophils of patients and controls had a similar capacity to eliminate Streptococcus pneumoniae. Also, levels of activation markers (CD66b, CD11b, CD62L) in granulocytes and monocytes, phorbol ester- and zymosan-induced neutrophil oxygen radical production were not different between patients and controls. No differences in (anti-)oxidant status were found, except for higher concentrations of oxidized glutathione and lower plasma selenium and vitamin C in patients compared to controls. CONCLUSION: Compromised innate immune function does not seem to explain the increased risk for infectious complications in HPN patients using olive oil-based lipid emulsions.

Avaliação da atividade antimicrobiana de extratos de Eugenia anomala e Psidium salutare (Myrtaceae) frente à Escherichia coli e Listeria monocytogenes / Evaluation of the antimicrobial activity of extracts of Eugenia anomala and Psidium salutare (Myrtaceae) against the Escherichia coli and Listeria monocytogenes

RESUMO As doenças transmitidas por alimentos ocorrem principalmente devido à ingestão de alimentos contaminados por microrganismos patogênicos, dentre eles a Escherichia coli e Listeria monocytogenes. Uma das alternativas estudadas para minimizar a contaminação de alimentos é o emprego de plantas, ou seus extratos, como agentes antimicrobianos de origem natural em produtos alimentícios. Desta forma o objetivo do presente estudo é fornecer dados científicos a respeito de duas plantas nativas do RS ainda não estudadas, Eugenia anomala e Psidium salutare, visando potencial emprego como agente antimicrobiano natural em alimentos. Para tanto, avaliou-se a atividade antimicrobiana de extratos de E. anomala e P. salutare contra E. coli e L. monocytogenes através da determinação da concentração inibitória mínima (CIM) pelo método de microdiluição em caldo, a capacidade antioxidante dos extratos por meio do método de redução do radical DPPH e a citotoxicidade in vitro empregando células CHO-K1. Os resultados obtidos mostraram que os extratos de acetato de etila e etanólico de ambas as espécies possuem ação antioxidante muito alta, de 94,08% e 93,86%, respectivamente. Apenas o extrato hexânico de P. salutare apresentou ação antimicrobiana moderada (CIM = 312,5 µg/mL). Todos os extratos apresentaram ação citotóxica sendo que os maiores percentuais foram do extrato clorofórmico de E. anomala (77,05%) e hexânico de P. salutare (76,79%), na concentração de 100 µg/mL. Assim, o presente estudo demonstrou que as espécies vegetais estudadas apresentam potencial para emprego como agente antimicrobiano destes microrganismos.

ABSTRACT The foodborne diseases occur mainly due to the ingestion of food contaminated by pathogenic microorganisms, including Escherichia coli and Listeria monocytogenes. One of the alternatives studied to minimize contamination of food is the use of plants or their extracts as antimicrobial agents naturally occurring in food products. The objective of this study is to provide scientific data on two native plants of RS have not studied Eugenia anomala and Psidium salutare for a potential use as a natural antimicrobial agent in food. To this end, we evaluated the antimicrobial activity of extracts of E. anomala and P. salutare against E. coli and L. monocytogenes by determining the minimum inhibitory concentration (MIC) by the broth microdilution method, the antioxidant capacity of the extract for means DPPH radical reduction method and in vitro cytotoxicity using CHO-K1 cells. The results showed that the ethyl acetate and ethanolic extracts of both species have very high antioxidant activity, of 94.08% and 93.86%, respectively. Only the hexane extract of P. salutare showed a moderate antimicrobial activity (MIC = 312.5 mg/mL). Moreover, all extracts showed cytotoxic action of which the highest percentages were the chloroform extract of E. anomala (77.05%) and hexane P. salutare (76.79%) at a concentration of 100 mg/mL. Thus, the present study showed that plant species have potential for use as an antimicrobial agent against these microorganisms.

Molten carbonate fuel cells fed with biogas: combating H(2)S.

The use of biomass and waste to produce alternative fuels, due to environmental and energy security reasons, is a high-quality solution especially when integrated with high efficiency fuel cell applications. In this article we look into the coupling of an anaerobic digestion process of organic residues to electrochemical conversion to electricity and heat through a molten carbonate fuel cell (MCFC). In particular the pathway of the exceedingly harmful compound hydrogen sulphide (H(2)S) in these phases is analysed. Hydrogen sulphide production in the biogas is strongly interrelated with methane and/or hydrogen yield, as well as with operating conditions like temperature and pH. When present in the produced biogas, this compound has multiple negative effects on the performance and durability of an MCFC. Therefore, there are important issues of integration to be solved. Three general approaches to solve the sulphur problem in the MCFC are possible. The first is to prevent the formation of hydrogen sulphide at the source: favouring conditions that inhibit its production during fermentation. Secondly, to identify the sulphur tolerance levels of the fuel cell components currently in use and develop sulphur-tolerant components that show long-term electrochemical performance and corrosion stability. The third approach is to remove the generated sulphur species to very low levels before the gas enters the fuel cell.

Experimental progressive muscular dystrophy and its treatment with high doses anabolizing agents.

We are still a long way from discovering an unequivocal pathogenetic interpretation of progressive muscular dystrophy in man. Noteworthy efforts have been made in the experimental field; a recessive autosomic form found in the mouse seems to bear the closest resemblance to the human form from the genetic point of view. Myopathy due to lack of vitamin E and myopathy induced by certain viruses have much in common anatomically and pathologically with the human form. The authors induced myodystrophy in the rat by giving it a diet lacking in vitamin E. The pharmacological characteristics of vitamin E and the degenerative changes brought about by its deficiency, especially in the muscles, are illustrated. It is thus confirmed that the histological characteristics of myopathic rat muscle induced experimentally are extraordinarily similar to those of human myopathy as confirmed during biopsies performed at the Orthopaedic Traumatological Centre, Florence. The encouraging results obtained in various authoratative departments in myopathic patients by using anabolizing steroids have encouraged the authors to investigate the beneficial effects of one anabolizing agent (Dianabol, CIBA) at high doses in rats rendered myopathic by a diet deficient in vitamin E. In this way they obtained appreciable changes in body weight (increased from 50 to 70 g after forty days at a dose of 5 mg per day of anabolizing agent), but most of all they found histological changes due to "regenerative" changes in the muscle tissue, which however maintained its myopathic characteristics in the control animals that were not treated with the anabolizing agent. The authors conclude by affirming the undoubted efficacy of the anabolizing steroids in experimental myopathic disease, but they have reservations as to the transfer of the results into the human field, where high dosage cannot be carried out continuously because of the effects of the drug on virility; because the tissue injury too often occurs at an irreversible stage vis-a-vis the "regeneration" of the muscle tissue; and finally because the dystrophic injurious agent is certainly not the lack of vitamin E but something as yet unknown.

Inactivation of solubilised fusicoccin-binding sites by endogenous plant hydrolases.

The poor stability of crude solutions of fusicoccin-binding sites, prepared from acetonedried microsomal fractions of spinach leaves, results from the attack by endogenous phosphatase and α-mannosidase. The addition of either of these enzymes to solubilised binding sites preincubated with [(3)H]fusicoccin promptly releases most of the bound radioactivity. A satisfactory stabilization of the crude preparations is obtained with fluoride added either during homogenization of the tissue, or immediately after solubilisation. The results indicate that the fusicoccin-binding sites are phosphorylated glycoproteins.

Human primary T lymphocytes have a low capacity to amplify MLV-based amphotropic RCR and the virions produced are largely noninfectious.

The presence of replication-competent retrovirus (RCR) in retroviral-based gene therapy products poses a potential safety risk for patients. Therefore, RCR testing of clinical gene therapy products and monitoring of patients enrolled in gene therapy trials is required to assure viral safety. The requirement to test ex vivo-transduced cells originates from the presumed amplification of adventitious RCR during the transduction procedure. However, data on the capacity of different cell types to do so are lacking. In this study, we sought to analyze the amplification potential of primary human T lymphocytes after infection with amphotropic MLV-based RCR. The total number of viral particles produced after 1 or 2 weeks was measured by a quantitative 4070A env-specific RT-PCR assay. The fraction of infectious replication-competent viral particles was analyzed in the PG-4 S+L- assay. From this study, we conclude that the total number of viral particles RCR produced by T lymphocytes is 2-4 logs lower than the number produced by NIH-3T3 cells. Surprisingly, less than 1% of the viral particles produced by primary T lymphocytes appeared to be infectious, while nearly all virions produced by NIH-3T3 were. We conclude that primary human T lymphocytes are low producers of MLV-based amphotropic RCR.