Liposome-based dry powder vaccine immunization targeting the lungs induces broad protection against pneumococcus.

Streptococcus pneumoniae is an important human pathogen. Currently used conjugate vaccines are effective against invasive disease, but protection is restricted to serotypes included in the formulation, leading to serotype replacement. Furthermore, protection against non-invasive disease is reported to be considerably lower. The development of a serotype-independent vaccine is thus important and Pneumococcal surface protein A (PspA) is a promising vaccine candidate. PspA shows some diversity and can be classified in 6 clades and 3 families, with families 1 and 2 being the most frequent in clinical isolates. The ideal vaccine should thus induce protection against the two most common families of PspA. The aim of this work was to develop a liposome-based vaccine containing PspAs from family 1 and 2 and to characterize its immune response. Liposomes (LP) composed of dipalmitoylphosphatidylcholine (DPPC) and 3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) with or without α-galactosylceramide (α-GalCer) were produced by microfluidics, encapsulating PspA from clade 1 (PspA1, family 1) and/or clade 4 (PspA4Pro, family 2) followed by spray-drying with trehalose to form nanocomposite microparticles carriers (NCMP). LP/NCMPs showed good stability and preservation of protein activity. LP/NCMPs containing PspA1 and/or PspA4Pro were used for immunization of mice targeting the lungs. High serum IgG antibody titers against both PspA1 and PspA4Pro were detected in animals immunized with LP/NCMPs containing α-GalCer, with a balance of IgG1 and IgG2a titers. IgG in sera from immunized mice bound to pneumococcal strains from different serotypes and expressing different PspA clades, indicating broad recognition. Mucosal IgG and IgA were also detected. Importantly, immunization with LP/NCMPs induced full protection against strains expressing PspAs from family 1 and 2. Furthermore, CD4+ resident memory T cells were detected in the lungs of the immunized animals that survived the challenge.

Erythrocyte-derived liposomes for the treatment of inflammatory diseases.

Effective and safe therapies to counteract persistent inflammation are necessary. We developed erythrocyte-derived liposomes (EDLs) with intrinsic anti-inflammatory activity. The EDLs were prepared using lipids extracted from erythrocyte membranes, which are rich in omega-3 fatty acids with several health benefits. Diclofenac, a widely used anti-inflammatory drug, was incorporated into EDLs in relevant therapeutic concentrations. The EDLs were also functionalised with folic acid to allow their active targeting of M1 macrophages, which are key players in inflammatory processes. In the presence of lipopolysaccharide (LPS)-stimulated macrophages, empty EDLs and EDLs incorporating diclofenac were able to reduce the levels of important pro-inflammatory cytokines, namely interleukin-6 (IL-6; ≈85% and 77%, respectively) and tumour necrosis factor-alpha (TNF-α; ≈64% and 72%, respectively). Strikingly, cytocompatible concentrations of EDLs presented similar effects to dexamethasone, a potent anti-inflammatory drug, in reducing IL-6 and TNF-α concentrations, demonstrating the EDLs potential to be used as bioactive carriers in the treatment of inflammatory diseases.

Chemical composition of essential oils from the apiaceae family, cytotoxicity, and their antifungal activity in vitro against candida species from oral cavity / Composição química de óleos essenciais da família apiaceae, citotoxicidade e sua atividade antifúngica in vitro contra espécies de candida da cavidade oral

Abstract The aims of this research were: evaluate the chemical composition and the cytotoxicity of the Cuminum cyminum (cumin), Anethum graveolens (dill), Pimpinella anisum (anise) and Foeniculum vulgare (fennel) essential oils, as well as their antifungal activity in vitro against ten Candida spp. isolates. The chemical composition of the oils was analyzed by means of gas chromatography coupled with mass spectrometry (GC/MS). The cytotoxicity assays were performed, using the cell proliferation reagent WST-1 in L929 mouse fibroblasts (20x103 well-1). The determinate the Minimum Inhibitory Concentration (MIC), was performed through the Broth Microdilution technique (CLSI). The chemical main components were the cuminaldehyde (32.66%) for cumin, carvone (34.89%) for the dill, trans-anethole (94.01%) for the anise and anethole (79.62%) for the fennel. Anise and fennel did not were cytotoxic in all the tested concentrations, however the cumin oil was cytotoxic in the concentration of 20 mg.mL-1 and the dill in the concentrations of 20 and 8 mg.mL-1. All yeasts were susceptible against the evaluated essential oils. Cumin presented the lowest MIC against yeasts. We concluded that all the essential oils presented inhibitory action against Candida spp., and C . cyminum, P. anisum and F. vulgare were not cytotoxic in the same minimum inhibitory concentrations for the fungi.

Resumo Os objetivos desta pesquisa foram: avaliar a composição química e a citotoxicidade dos óleos essenciais de Cuminum cyminum (cominho), Anethum graveolens (endro), Pimpinella anisum (erva-doce) e Foeniculum vulgare (funcho), bem como sua atividade antifúngica in vitro contra dez isolados de Candida spp.. A composição química dos óleos foi analisada por meio de cromatografia gasosa acoplada à espectrometria de massa (GC / MS). Os ensaios de citotoxicidade foram realizados, utilizando o reagente de proliferação celular WST-1 em fibroblastos de ratinho L929 (20x103 poço-1). A determinação da Concentração Inibitória Mínima (MIC) foi realizada através da técnica de microdiluição em caldo (CLSI). Os principais componentes químicos foram o cuminaldeído (32.66%) para cominho, carvona (34.89%) para o endro, trans-anetol (94.01%) para erva-doce e anetol (79.62%) para a funcho. O endro e a erva-doce não foram citotóxicos em todas as concentrações testadas, no entanto, o óleo de cominho foi citotóxico na concentração de 20 mg.mL-1 e o endro nas concentrações de 20 e 8 mg.mL-1. Todas as leveduras foram suscetíveis aos óleos essenciais avaliados. O cominho apresentou a menor CIM contra as leveduras. Concluímos que todos os óleos essenciais apresentaram ação inibidora contra Candida spp., e C. cyminum, P. anisum e F. vulgare não foram citotóxicos nas mesmas concentrações inibitórias mínimas para os fungos.

Chemical composition of essential oils from the apiaceae family, cytotoxicity, and their antifungal activity in vitro against candida species from oral cavity.

The aims of this research were: evaluate the chemical composition and the cytotoxicity of the Cuminum cyminum (cumin), Anethum graveolens (dill), Pimpinella anisum (anise) and Foeniculum vulgare (fennel) essential oils, as well as their antifungal activity in vitro against ten Candida spp. isolates. The chemical composition of the oils was analyzed by means of gas chromatography coupled with mass spectrometry (GC/MS). The cytotoxicity assays were performed, using the cell proliferation reagent WST-1 in L929 mouse fibroblasts (20x103 well-1). The determinate the Minimum Inhibitory Concentration (MIC), was performed through the Broth Microdilution technique (CLSI). The chemical main components were the cuminaldehyde (32.66%) for cumin, carvone (34.89%) for the dill, trans-anethole (94.01%) for the anise and anethole (79.62%) for the fennel. Anise and fennel did not were cytotoxic in all the tested concentrations, however the cumin oil was cytotoxic in the concentration of 20 mg.mL-1 and the dill in the concentrations of 20 and 8 mg.mL-1. All yeasts were susceptible against the evaluated essential oils. Cumin presented the lowest MIC against yeasts. We concluded that all the essential oils presented inhibitory action against Candida spp., and C . cyminum, P. anisum and F. vulgare were not cytotoxic in the same minimum inhibitory concentrations for the fungi.

On-line prediction of the feeding phase in high-cell density cultivation of rE. coli using constructive neural networks.

Streptococcus pneumoniae (pneumococcus) is a bacterium responsible for a wide spectrum of illnesses. The surface of the bacterium consists of three distinctive membranes: plasmatic, cellular and the polysaccharide (PS) capsule. PS capsules may mediate several biological processes, particularly invasive infections of human beings. Prevention against pneumococcal related illnesses can be provided by vaccines. There is a sound investment worldwide in the investigation of a proteic antigen as a possible alternative to pneumococcal vaccines based exclusively on PS. A few proteins which are part of the membrane of the pneumococcus seem to have antigen potential to be part of a vaccine, particularly the PspA. A vital aspect in the production of the intended conjugate pneumococcal vaccine is the efficient production (in industrial scale) of both, the chosen PS serotypes as well as the PspA protein. Growing recombinant Escherichia coli (rE. coli) in high-cell density cultures (HCDC) under a fed-batch regime requires a refined continuous control over various process variables where the on-line prediction of the feeding phase is of particular relevance and one of the focuses of this paper. The viability of an on-line monitoring software system, based on constructive neural networks (CoNN), for automatically detecting the time to start the fed-phase of a HCDC of rE. coli that contains a plasmid used for PspA expression is investigated. The paper describes the data and methodology used for training five different types of CoNNs, four of them suitable for classification tasks and one suitable for regression tasks, aiming at comparatively investigate both approaches. Results of software simulations implementing five CoNN algorithms as well as conventional neural networks (FFNN), decision trees (DT) and support vector machines (SVM) are also presented and discussed. A modified CasCor algorithm, implementing a data softening process, has shown to be an efficient candidate to be part of an on-line HCDC monitoring system for detecting the feeding phase of the HCDC process.

Pneumococcal whole-cell vaccine: optimization of cell growth of unencapsulated Streptococcus pneumoniae in bioreactor using animal-free medium.

The high cost of the available pneumococcal conjugated vaccines has been an obstacle in implementing vaccination programs for children in developing countries. As an alternative, Malley et al. proposed a vaccine consisting of inactivated whole-cells of unencapsulated S. pneumoniae, which provides serotype-independent protection and involves lower production costs. Although the pneumococcus has been extensively studied, little research has focused on its large-scale culture, thus implying a lack of knowledge of process parameters, which in turn are essential for its successful industrial production. The strain Rx1Al- eryR was originally cultured in Todd-Hewitt medium (THY), which is normally used for pneumococcus isolation, but is unsuitable for human vaccine preparations. The purposes of this study were to compare the strains Rx1Al- eryR and kanR, develop a new medium, and generate new data parameters for scaling-up the process. In static flasks, cell densities were higher for eryR than kanR. In contrast, the optical density (OD) of the former decreased immediately after reaching the stationary phase, and the OD of the latter remained stable. The strain Rx1Al- kanR was cultivated in bioreactors with medium based on either acid-hydrolyzed casein (AHC) or enzymatically hydrolyzed soybean meal (EHS). Biomass production in EHS was 2.5 times higher than in AHC, and about ten times higher than in THY. The process developed for growing the strain Rx1Al- kanR in pH-controlled bioreactors was shown to be satisfactory to this fastidious bacterium. The new culture conditions using this animal-free medium may allow the production of the pneumococcal whole-cell vaccine.

Postural control of small for gestational age infants born at term

OBJECTIVE: This study compared the postural control of small (SGA) and appropriate (AGA) for gestational age infants born at term, at the ages of 3, 6, 9 and 12 months. METHOD: This was a cohort study of infants born at term, with birth weight less than the 10th percentile for the SGA group and between the 10th and 90th percentiles for the AGA group. Infants with genetic syndromes, malformations, congenital infections and internment in neonatal intensive care unit were excluded. The evaluation instrument was the Alberta Infant Motor Scale. RESULTS: Comparison of the SGA and AGA groups did not show any significant differences (p>0.05) at the assessment times. However, the postural control of the SGA group was influenced by the gestational age (r=-0.83; p= 0.006) and 5th minute Apgar (r= 0.79; p= 0.01) in the 3rd month, and by maternal occupation (r= 0.67; p= 0.01) in the 6th month. CONCLUSION: It was concluded that the postural control was similar in the groups. However, the postural control of the SGA group was influenced by biological and environmental factors.

OBJETIVO: Este estudo teve por objetivo comparar o controle postural de lactentes nascidos a termo, pequenos (PIG) e adequados para a idade gestacional (AIG) nos 3º, 6º, 9º e 12º meses. MÉTODO: Estudo longitudinal de lactentes nascidos a termo, com peso de nascimento menor que o percentil 10 para o grupo PIG e entre o percentil 10 e 90 para o grupo AIG. Síndromes genéticas, más-formações, infecções congênitas e internados em unidade de terapia intensiva neonatal foram excluídos. O instrumento de avaliação foi Alberta Infant Motor Scale. RESULTADOS: A comparação do grupo PIG e AIG não mostrou diferença significativa (p> 0,05) nos meses avaliados. Entretanto, o controle postural do grupo PIG foi influenciado pela idade gestacional (r= -0,83/p= 0,006) e Apgar de 5' (r= 0,79/p= 0,01) no 3º mês; e pela ocupação materna (r= 0,67/p= 0,01) no 6º mês. CONCLUSÃO: Concluiu-se que o controle postural foi similar nos grupos; porém o controle postural do grupo PIG foi influenciado por fatores biológicos e ambientais.

Introduction of air in the anaerobic culture of Streptococcus pneumoniae serotype 23F induces the release of capsular polysaccharide from bacterial surface into the cultivation medium.

AIM: An approach to increase Streptococcus pneumoniae capsular polysaccharide (CPS) in the culture medium during fed-batch cultivation in bioreactor. METHODS AND RESULTS: Streptococcus pneumoniae serotype 23F was cultivated in a 5-l bioreactor with nitrogen-sparging and followed by addition of air in the stationary phase. The amount of CPS released in the supernatant progressively increased under air sparging. The profile of cellular viability and optical density was similar in both cultures. Immunoelectron microscopy showed that the amount of tightly cell-bound CPS was higher in bacteria cultivated under nitrogen than under air. CONCLUSIONS: The stress caused by the addition of air at the stationary phase promoted a large increase of free CPS into the medium, as a consequence of the morphologic change in the capsule. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of air in the stationary phase of the culture would greatly simplify the subsequent downstream process, allowing CPS purification from the supernatant. The direct consequence of this process improvement is the reduction of vaccine production costs.

Accumulation of organic acids in cultivations of Neisseria meningitidis C

Aiming at the industrial production of serogroup C meningococcal vaccine, different experimental protocols were tested to cultivate Neisseria meningitidis C and to investigate the related organic acid release. Correlations were established between specific rates of acetic acid and lactic acid accumulation and specific growth rate, during cultivations carried out on the Frantz medium in a 13 l bioreactor at 35°C, 0.5 atm, 400 rpm and air flowrate of 2 l min-1. A first set of nine batch runs was carried out: (1) with control of dissolved oxygen (O2) at 10% of its saturation point, (2) with control of pH at 6.5, and (3) without any control, respectively. Additional fed-batch or partial fed-batch cultivations were performed without dissolved O2 control, varying glucose concentration from 1.0 to 3.0 g l -1, nine of which without pH control and other two with pH control at 6.5. No significant organic acid level was detected with dissolved O 2 control, whereas acetic acid formation appeared to depend on biomass growth either in the absence of any pH and dissolved O2 control or when the pH was kept at 6.5. Under these last conditions, lactic acid was released as well, but it did not seem to be associated to biomass growth. A survey of possible metabolic causes of this behavior suggested that N. meningitidis may employ different metabolic pathways for the carbon source uptake depending on the cultivation conditions.

Comparative study of clinical characteristics of neutropenic and non-neutropenic adult cancer patients with bloodstream infections.

A total of 399 consecutive episodes of bloodstream infections in adult patients with haematologic malignancies and solid tumours were evaluated prospectively over a 26-month period, with the aim of determining the clinical characteristics and the microbiological profile of the patients relative to neutrophil count. The overall 30-day mortality rate was 32% (35% in non-neutropenic patients vs. 26% in neutropenic patients, p=0.05). Main diagnoses were solid tumours (33%) and lymphoma (29%). Most of the episodes of bloodstream infection (58%) occurred in non-neutropenic patients. Acute leukaemia and bone marrow transplantation predominated in the neutropenic group. Non-neutropenic patients tended to be older and to have a higher frequency of solid tumours and advanced or uncontrolled diseases. Indwelling central venous catheters were present in 51% of the episodes, with a predominance of long-term catheters in neutropenic haematologic patients. Concomitant infections were observed more frequently in non-neutropenic patients. There were 1,040 noninfectious comorbid conditions, most of which were present in non-neutropenic patients. The causative pathogens were predominantly gram-negative bacilli (56%). Escherichia coli and Klebsiella pneumoniae were isolated more frequently from neutropenic patients, while Staphylococcus aureus and Acinetobacter spp. were more frequent in non-neutropenic patients. Seventy-four percent of the episodes of candidaemia occurred in patients with central venous catheters, with non-albicans strains predominating. The results of this study highlight the heterogeneity of cancer patients with bloodstream infections and the value of stratifying risk factors and aetiologic agents according to neutrophil count.

Introduction of air in the anaerobic culture of Streptococcus pneumoniae serotype 23F induces the release of capsular polysaccharide from bacterial surface into the cultivation medium

Aim: An approach to increase Streptococcus pneumoniae capsular polysaccharide (CPS) in the culture medium during fed-batch cultivation in bioreactor. Methods and Results: Streptococcus pneumoniae serotype 23F was cultivated in a 5-l bioreactor with nitrogen-sparging and followed by addition of air in the stationary phase. The amount of CPS released in the supernatant progressively increased under air sparging. The profile of cellular viability and optical density was similar in both cultures. Immunoelectron microscopy showed that the amount of tightly cell-bound CPS was higher in bacteria cultivated under nitrogen than under air. Conclusions: The stress caused by the addition of air at the stationary phase promoted a large increase of free CPS into the medium, as a consequence of the morphologic change in the capsule. Significance and Impact of the Study: The use of air in the stationary phase of the culture would greatly simplify the subsequent downstream process, allowing CPS purification from the supernatant. The direct consequence of this process improvement is the reduction of vaccine production costs.

Influência de práticas maternas no desenvolvimento motor de lactentes do 6º ao 12º meses de vida / Influence of child-rearing practices on infants' motor development between the sixth and twelfth months of life

CONTEXTO: Práticas maternas são comportamentos específicos, por meio dos quais as mães/cuidadores desempenham suas tarefas maternais. Estas práticas poderiam influenciar o desenvolvimento motor de lactentes. OBJETIVO: verificar a influência de práticas maternas, utilizadas no cuidado diário de lactentes saudáveis, sobre seu desenvolvimento motor do 6° ao 12° meses de vida. MÉTODO: Selecionados 14 lactentes, nascidos a termo e saudáveis, avaliados longitudinalmente no 6°, 9° e 12° meses de vida, utilizando-se a Alberta Infant Motor Scale. Em cada avaliação/idade a mãe respondeu a um questionário fechado sobre práticas, predominantemente adotadas no cuidado diário do lactente durante os períodos de vigília. Considerou-se neste estudo a postura predominantemente adotada pelo lactente, local preferencial de permanência e a forma de carregar o lactente no colo. RESULTADOS: No 9° mês de vida o desempenho motor dos lactentes foi influenciado positivamente pela predominância na postura de quatro apoios, em relação à sentada e prono ou supino e pela permanência no chão em relação ao carrinho de bebê. No 12° mês houve influência positiva da predominância na postura de quatro apoios e em pé. A postura predominante no 6° mês de vida e a forma de carregar o lactente no 6°, 9° e 12° meses de vida não influenciaram o desempenho motor do grupo estudado. CONCLUSÃO: Os resultados sugerem que as práticas que estimulam a adoção da postura de quatro apoios e a utilização do chão como local de permanência influenciam positivamente o desenvolvimento motor de lactentes saudáveis a partir do 6° mês de vida.

Influência do baixo peso ao nascer sobre o desempenho motor de lactentes a termo no primeiro semestre de vida / Influence of the low birth weight on motor performance of term infants in the first semester of life

Este estudo teve por objetivo verificar a repercussao do baixo peso ao nascer (BPN) no desempenho motor, no primeiro semestre de vida, lactentes nascidos a termo, pequenos para a idade gestacional (PIG) comparando esses com um grupo -controle nascido com peso adequado para a idade gestacional (AIG). Para verificar a influencia do BPN sobre o desenvolvimento motor foramexcluidas da amostra a prematuridade e as patologias diagnosticadas ao nascimento. Tratou-se de um estudo de corte seccional e duplo-cego, no 3o. e no 6o. mes de vida. O desempenho motor foi mensurado com a Alberta Infant Motor Scale, a qual classifica os lactentesem uma curva de desenvolvimento, que varia entre o percentil 5 e 90. Para comparar os grupos foi utilizado o teste F para as variancias e o teste t para as medias (nivel de significancia fixado em 5 (por cento). No 3o. mes, o grupo PIG apresentou percentil medio inferior ao grupo AIG, no entanto, tal diferenca nao foi significativa. No 6o. mes, o perecentil medio do grupo AIG foi maior que o do grupo PIG, com diferenca significativa (p<0,05). Ambos os grupos de lactentes apresentaram instabilidade na aquisicao da motricidade e percentil medio inferior ao grupo normativo canadense (50 por cento). Conclui-se, entao, que o peso de nascimento pode ter influenciado a performance motora dos grupos, favorecendo o grupo AIG. Os resultados contribuirao para o diagnostico precoce de alteracoes motoras, bem como para o conhecimento dos fatores de risco para o desenvolvimento infantil

Prospective evaluation of the epidemiology, microbiology, and outcome of bloodstream infections in adult surgical cancer patients.

The aim of this study was to describe the epidemiology and microbiology of bloodstream infections (BSIs) among adult surgical cancer patients and to determine independent factors that influence in-hospital mortality. The study enrolled 112 consecutive episodes of BSIs in adult surgical cancer patients during a 26-month period. The median age of the patients was 64.5 years, and crude in-hospital mortality was 19.6%. The median time from surgery to the index blood culture was 11 days and from index blood culture to death was 4.5 days. Seventy-five percent of the patients had an advanced tumor disease, 36.6% were under intensive care, and 68.7% had a central venous catheter in place at the time the bloodstream infection was diagnosed. Associated infected sites were present in 57.1% of the episodes. There were 328 noninfectious co-morbid conditions. Poor performance status, weight loss, hypoalbuminemia, and ventilatory support accounted for 67.4% of them. There was a predominance of aerobic gram-negative bacilli (62%), followed by gram-positive cocci (26.6%) and fungi (9.3%). The observed mortality rates associated with these organism groups were similar (23.6% vs 15% vs 28.6%, respectively; P=0.44). The most frequent organisms were Enterobacter spp., coagulase-negative staphylococci, Klebsiella spp., Acinetobacter spp., and fungi. Nonfermentative strains predominated in patients with catheters. Thirty-five (30.2%) pathogens were considered resistant. There was no significant difference in the mortality rate between patients with resistant and those with nonresistant organisms (20% vs 26%, respectively; P=0.49). Logistic regression analysis showed > or = 4 co-morbid conditions, advanced tumor, thoracic surgery, catheter retention, and pulmonary infiltrates as independent predictors of mortality. Medical and infection control measures addressing certain variables amenable to intervention might reduce the negative impact of postoperative infectious morbidity and mortality of BSIs in adult surgical cancer patients.

Bloodstream infection surveillance in a cancer centre: a prospective look at clinical microbiology aspects.

A prospective clinical and microbiological surveillance study was conducted during a 26-month period to evaluate consecutive malignancy or post-bone marrow transplant patients with positive blood cultures. The study included 859 episodes of bloodstream infection (BSI) in 719 patients. There were 6.9 BSI episodes/1000 patient-days. Overall mortality was 25%. The median age of patients was 43 years, with 71% of episodes occurring in patients aged > 18 years. Patients with underlying haematology malignancies accounted for 38.2% of the episodes. An indwelling central vein catheter was present in 61% of episodes. BSI origin was unknown in 27% of episodes, associated with other sites in 49.6%, and catheter-related in 23.4%. There were 638 concomitant infection sites, of which the most common were pulmonary (28.4%), urinary tract (14.8%), and non-surgical skin or soft tissue (9.7%). In total, 1039 microorganisms were isolated within 48 h of the first blood culture, of which Gram-negative bacilli accounted for 56%. Among Klebsiella pneumoniae and Escherichia coli isolates, 37.8% and 8.9%, respectively, produced extended-spectrum beta-lactamases. High rates of ceftazidime resistance were detected among Acinetobacter spp. (40%) and Enterobacter spp. (51.2%). E. coli and K. pneumoniae were isolated frequently from haematology patients, and Enterobacter spp. from solid tumour patients. E. coli, K. pneumoniae and Pseudomonas aeruginosa were isolated more often from neutropenic than from non-neutropenic patients. Oxacillin resistance was detected in 18.7% of Staphylococcus aureus isolates. It was concluded that continuous multidisciplinary surveillance of BSI is warranted in this high-risk group of patients in order to develop strategies for antimicrobial resistance control and treatment of infectious complications.

Prospective evaluation of the epidemiology, microbiology, and outcome of bloodstream infections in hematologic patients in a single cancer center.

Bloodstream infections (BSIs) have an important impact on the outcome of cancer patients. A prospective cohort study was undertaken at a referral cancer center in order to describe the clinical and microbiological characteristics of patients with hematologic malignancies and BSIs and to identify independent predictors associated with mortality. The study enrolled 110 consecutive BSI episodes during an 18-month period. Patients were monitored for 30 days after the last positive blood culture. There were 10.24 BSI episodes per 1,000 patient-days. The median age of the patients was 25 years. Most patients had acute leukemia ( n=72). The origin of the BSI was unknown in 43.6% of the episodes and was associated with known sites in 32.7%. There were 58 concomitant infectious sites (lungs, 43%, and soft tissue, 22.4%) and 195 noninfectious comorbid factors (poor performance status, 30.2%; undernourishment, 14.3%). The median neutrophil count was 215 cells/mm(3). Indwelling catheters were present in 70% of the episodes. The majority of isolates obtained within the first 48 h of the BSI episode (61%) were gram-negative rods. Overall mortality was 24.5%. Multivariate analysis using logistic regression showed relapsed leukemia, poor performance status, recent weight loss, and ventilatory failure requiring ventilatory support as independent predictors of mortality. Hematologic cancer patients with BSIs should be regarded as a distinct group of patients at high risk of death. The knowledge of variables amenable to intervention would help diminish or prevent serious medical complications.

Optimization of medium and cultivation conditions for capsular polysaccharide production by Streptococcus pneumoniae serotype 23F.

The influence of medium composition and culture conditions on Streptococcus pneumoniae serotype 23F cultivation was investigated in order to develop an industrial method for polysaccharide (PS) production. Acid-hydrolyzed casein (AHC) and dialyzed enzymatically hydrolyzed soybean meal (EHS) were investigated as nitrogen sources, and the vitamin solution of Hoeprich's medium and dialyzed yeast extract as vitamin sources. The influence of initial glucose concentration was also evaluated. In flask experiments, the best nitrogen source for PS production was AHC; EHS yielded small amounts of PS without interfering with bacterial growth. Dialyzed yeast extract provided an approximately 2-fold increase in PS production when compared to Hoeprich's vitamin solution. In a 5-l bioreactor, it was observed that the pneumococcus did not grow under aerobic conditions, CO(2) did not increase PS yield, glucose was inhibitory above 30 g l(-1), and the main glucose catabolism product was lactate, which had an inhibitory effect on cell growth. When anaerobic cultivation was performed under N(2) flow using the optimized medium, 240 mg l(-1) of soluble PS was obtained, which represents a 3-fold increase in yield as compared to that described in the published patent [Yavordios and Cousin (1983) European Patent 0 071515 A1]. Application of these results would considerably simplify upstream and downstream processes for PS production.

Optimization of medium and cultivation conditions for capsular polysaccharide production by Streptococcus pneumoniae serotype 23F

The influence of medium composition and culture conditions on Streptococcus pneumoniae serotype 23F cultivation was investigated in order to develop an industrial method for polysaccharide (PS) production. Acid-hydrolyzed casein (AHC) and dialyzed enzymatically hydrolyzed soybean meal (EHS) were investigated as nitrogen sources, and the vitamin solution of Hoeprich's medium and dialyzed yeast extract as vitamin sources. The influence of initial glucose concentration was also evaluated. In flask experiments, the best nitrogen source for PS production was AHC; EHS yielded small amounts of PS without interfering with bacterial growth. Dialyzed yeast extract provided an approximately 2-fold increase in PS production when compared to Hoeprich's vitamin solution. In a 5-l bioreactor, it was observed that the pneumococcus did not grow under aerobic conditions, CO2 did not increase PS yield, glucose was inhibitory above 30 g l-1, and the main glucose catabolism product was lactate, which had an inhibitory effect on cell growth. When anaerobic cultivation was performed under N2 flow using the optimized medium, 240 mg l-1 of soluble PS was obtained, which represents a 3-fold increase in yield as compared to that described in the published patent [Yavordios and Cousin (1983) European Patent 0 071515 A1]. Application of these results would considerably simplify upstream and downstream processes for PS production.

Motor development during the first year: a comparative study.

This investigation of the motor development characteristics of Brazilian infants during the 1st year of postnatal life compared the findings with those of a widely used U.S. sample (N. Bayley, 1993). Analysis of the 12 monthly assessments indicated that Brazilian infants' scores increased with age, with the greatest increase occurring over the first 8 months. As a general comparison, the results are similar to the U.S. patterns of development. However, the Brazilian sample exhibited mean scores significantly lower than the U.S. sample's in the 3rd, 4th, and 5th months. More specific analyses indicated that the difference within these months was on tasks of sitting and grasping. Possible explanations for the differences focus on variations in child-rearing practices and the influence of biological maturation in early movement behaviors.