Antifungal Distribution Into Cerebrospinal Fluid,Vitreous Humor,Bone, and Other Difficult Sites

The incidence of invasive fungal infections continues to increase, especially in patients with immune dysfunction. Fungal infections are often difficult to treat, requiring therapy for weeks or months to eradicate infection. Although fungal infections of the central nervous system, eye, and bones occur less frequently than infections at other sites, it is necessary to assess the utility of the currently available antifungal agents in treating these infections. Unfortunately, information regarding drug distribution to these sites is often scarce and limited to a few animal studies or case reports. This review summarizes information about commonly used antifungal agents and their penetration into the central nervous system, eye, and bone.     

The role of anaerobic bacteria in sinusitis

The normal oropharyngeal flora contained aerobic and anaerobic bacteria that can cause respiratory infections including sinusitis. Some of these bacteria can interfere with the growth of potential pathogens and may play a role in preventing infections. Anaerobic bacteria emerge as pathogens as the infection becomes chronic. This may be the result of the selective pressure of antimicrobial agents that enable resistant anaerobic organisms to survive, and from the development over time of conditions appropriate for anaerobic growth, which include the reduction in oxygen tension and an increase in acidity within the sinus cavity. Anaerobes were isolated in acute maxillary sinusitis of odontogenic origin and in over half of the patients with chronic sinusitis whenever proper techniques for their cultivation were employed. These organisms were also recovered in acute sinusitis that was associated with dental infections. The predominant isolates were pigmented Prevotella and Porphyromonas, Fusobacterium and Peptostreptococcus spp.     

Congenital viral infections of the brain: lessons learned from lymphocytic choriomeningitis virus in the neonatal rat

The fetal brain is highly vulnerable to teratogens, including many infectious agents. As a consequence of prenatal infection, many children suffer severe and permanent brain injury and dysfunction. Because most animal models of congenital brain infection do not strongly mirror human disease, the models are highly limited in their abilities to shed light on the pathogenesis of these diseases. The animal model for congenital lymphocytic choriomeningitis virus (LCMV) infection, however, does not suffer from this limitation. LCMV is a well-known human pathogen. When the infection occurs during pregnancy, the virus can infect the fetus, and the developing brain is particularly vulnerable. Children with congenital LCMV infection often have substantial neurological deficits. The neonatal rat inoculated with LCMV is a superb model system of human congenital LCMV infection. Virtually all of the neuropathologic changes observed in humans congenitally infected with LCMV, including microencephaly, encephalomalacia, chorioretinitis, porencephalic cysts, neuronal migration disturbances, periventricular infection, and cerebellar hypoplasia, are reproduced in the rat model. Within the developing rat brain, LCMV selectively targets mitotically active neuronal precursors. Thus, the targets of infection and sites of pathology depend on host age at the time of infection. The rat model has further shown that the pathogenic changes induced by LCMV infection are both virus-mediated and immune-mediated. Furthermore, different brain regions simultaneously infected with LCMV can undergo widely different pathologic changes, reflecting different brain region-virus-immune system interactions. Because the neonatal rat inoculated with LCMV so faithfully reproduces the diverse neuropathology observed in the human counterpart, the rat model system is a highly valuable tool for the study of congenital LCMV infection and of all prenatal brain infections In addition, because LCMV induces delayed-onset neuronal loss after the virus has been cleared, the neonatal rat infected with LCMV may be an excellent model system to study neurodegenerative or psychiatric diseases whose etiologies are hypothesized to be virus-induced, such as autism, schizophrenia, and temporal lobe epilepsy.     

The biology of cementum increments (with an archaeological application)

Cementum, a bone-like tissue that surrounds the roots of teeth, anchoring them to the periodontal ligament, is useful for determining the age at and season of death of mammals, an issue of concern for both archaeologists and biologists. When a tooth is sectioned and examined microscopically, cementum appears in bands that differ in their optical properties and are well correlated with seasonal growth. Because it is a continually deposited tissue that is rarely modified or resorbed, cementum records the history of a variety of seasonal factors that affect its growth. An understanding of the biological nature of cementum is crucial to the identification of these factors and interpretation of the resulting incremental structure. This paper outlines current knowledge of the development, histology and function of cementum in the context of the mammalian masticatory apparatus. Of the various types of cementum, acellular cementum is often more appropriate for seasonal correlations. Differences between acellular cementum increments are probably related to specific dietary factors that often vary between seasons. Cellular cementum increments probably result from phasic cementogenesis triggered by tooth eruption. This paper outlines a study of cementum bands in Gazella gazella for which there is an excellent correlation between the season of death and incremental structures in their cementum. This correlation can be used to estimate the season of death of gazelles from archaeological sites in the Levant. Problems for future research are outlined.     

Biogas production: current state and perspectives

Anaerobic digestion of energy crops, residues, and wastes is of increasing interest in order to reduce the greenhouse gas emissions and to facilitate a sustainable development of energy supply. Production of biogas provides a versatile carrier of renewable energy, as methane can be used for replacement of fossil fuels in both heat and power generation and as a vehicle fuel. For biogas production, various process types are applied which can be classified in wet and dry fermentation systems. Most often applied are wet digester systems using vertical stirred tank digester with different stirrer types dependent on the origin of the feedstock. Biogas is mainly utilized in engine-based combined heat and power plants, whereas microgas turbines and fuel cells are expensive alternatives which need further development work for reducing the costs and increasing their reliability. Gas upgrading and utilization as renewable vehicle fuel or injection into the natural gas grid is of increasing interest because the gas can be used in a more efficient way. The digestate from anaerobic fermentation is a valuable fertilizer due to the increased availability of nitrogen and the better short-term fertilization effect. Anaerobic treatment minimizes the survival of pathogens which is important for using the digested residue as fertilizer. This paper reviews the current state and perspectives of biogas production, including the biochemical parameters and feedstocks which influence the efficiency and reliability of the microbial conversion and gas yield.     

Urogenital, maternal and neonatal isolates of Haemophilus influenzae: identification of unusually virulent serologically non-typable clone families and evidence for a new Haemophilus species

A collection of 117 strains of Haemophilus influenzae, including 112 non-typable isolates recovered predominantly in the USA and France from genital, obstetric and neonatal sources, was characterized by the electrophoretic mobilities of 10 metabolic enzymes. Eighty-six distinctive multilocus chromosomal genotypes (electrophoretic types, ETs) were distinguished on the basis of allele profiles at the enzyme loci. Isolates of five allied biotype IV ETs were highly divergent from all other strains and hybridization of chromosomal DNA revealed that they undoubtedly represent a previously unrecognized species of Haemophilus. Isolates representing these ETs were recovered predominantly from obstetric infections and serious neonatal diseases and apparently possess specific tropism for the genital tract. Strains of these five ETs were present in samples from both the USA and France, but only in the USA did they cause bacteraemia and meningitis, an occurrence which probably reflects differences in patient management between the two countries. Although strains assigned to H. influenzae (sensu stricto) were strongly polymorphic in multilocus enzyme genotype, 69% of isolates recovered from patients with meningitis and/or septicaemia were assigned to only two clone families, a result suggesting that some serologically nontypable strains of H. influenzae originating from the genital tract are unusually virulent.     

The place of molecular genetic methods in the diagnostics of human pathogenic anaerobic bacteria. A minireview

Anaerobic infections are common and can cause diseases associated with severe morbidity, but are easily overlooked in clinical settings. Both the relatively small number of infections due to exogenous anaerobes and the much larger number of infections involving anaerobic species that are originally members of the normal flora, may lead to a life-threatening situation unless appropriate treatment is instituted. Special laboratory procedures are needed for the isolation, identification and susceptibility testing of this diverse group of bacteria. Since many anaerobes grow more slowly than the facultative or aerobic bacteria, and particularly since clinical specimens yielding anaerobic bacteria commonly contain several organisms and often very complex mixtures of aerobic and anaerobic bacteria, considerable time may elapse before the laboratory is able to provide a final report. Species definition based on phenotypic features is often time-consuming and is not always easy to carry out. Molecular genetic methods may help in the everyday clinical microbiological practice in laboratories dealing with the diagnostics of anaerobic infections. Methods have been introduced for species diagnostics, such as 16S rRNA PCR-RFLP profile determination, which can help to distinguish species of Bacteroides, Prevotella, Actinomyces, etc. that are otherwise difficult to differentiate. The use of DNA-DNA hybridization and the sequencing of special regions of the 16S rRNA have revealed fundamental taxonomic changes among anaerobic bacteria. Some anaerobic bacteria are extremely slow growing or not cultivatable at all. To detect them in special infections involving flora changes due to oral malignancy or periodontitis, for instance, a PCR-based hybridization technique is used. Molecular methods have demonstrated the spread of specific resistance genes among the most important anaerobic bacteria, the members of the Bacteroides genus. Their detection and investigation of the IS elements involved in their expression may facilitate following of the spread of antibiotic resistance among anaerobic bacteria involved in infections and in the normal flora members. Molecular methods (a search for toxin genes and ribotyping) may promote a better understanding of the pathogenic features of some anaerobic infections, such as the nosocomial diarrhoea caused by C. difficile and its spread in the hospital environment and the community. The investigation of toxin production at a molecular level helps in the detection of new toxin types. This mini-review surveys some of the results obtained by our group and others using molecular genetic methods in anaerobic diagnostics.     

Larval trematode infections in freshwater snails from the highveld and lowveld areas of Zimbabwe

Between November 1998 and October 2000, freshwater snails were collected monthly from the highveld and lowveld areas of Zimbabwe to determine the occurrence of larval trematodes. A total of 13,789 snails, representing ten species, were collected from 21 sites and 916 (6.6%) harboured patent trematode infections. Eight morphologically distinguishable types of cercariae were identified. Bulinus tropicus had the highest overall prevalence of infection (13.1%). The echinostome was the most common type of cercaria recovered, contributing 38.2% of all infections. Schistosoma cercariae were recovered mainly from the highveld and comprised 8.0% of all infections. Amphistome cercariae contributed 37.6% of all infections and were recorded from both the highveld and lowveld areas with a peak prevalence occurring during the post-rainy period (March-May). The main intermediate host for amphistomes was B. tropicus. Infections in B. globosus, B. forskalii and Biomphalaria pfeifferi with amphistome cercariae are new records for Zimbabwe.     

水霉菌的形态及ITS区分子鉴定

研究利用形态学和分子生物学相结合的方法, 对从患病黄颡鱼病灶处分离的水霉菌株(HSY)的分类地位进行了研究。结果显示, 该菌在18—23℃均能形成游动孢子囊, 但只在20℃才大量释放游动孢子; 在15℃培养约3 周出现大量的藏卵器, 多数顶生, 形态与Saprolegnia litoralis 和Saprolegnia ferax 的均非常相似。序列比对分析显示, HSY 菌株与S. litoralis、S. bulbosa、S. oliviae、S. longicaulis、S. ferax、S. mixta 和S.anomalies 的ITS 区(包括5.8S rDNA)序列相似性均高于99%。系统发育分析显示, 所选的真菌分为3 个群,HSY 落于第一个群, MP 树显示HSY 菌株与S. litoralis、S. bulbosa、S. oliviae、S. longicaulis、S. ferax 以及S. mixta 枝系均互相平行, 而NJ 树显示其与S. ferax 和S. mixta 更近。综合形态学、ITS 区序列及系统发育分析, 将HSY 菌株暂定为多子水霉(Saprolegnia ferax)。       

Is There Still a Place for Conventional Amphotericin B in the Treatment of Neonatal Fungal Infections?

Neonatal invasive fungal infections (IFIs) remain an increasing problem associated with high rates of morbidity and mortality, as well as late-onset neurodevelopmental implications. Invasive candidiasis remains the leading neonatal IFI. Candida albicans is the fungal species most often affecting this population, although a changing epidemiologic incidence to non-albicans Candida species is reported in some neonatal intensive care units. Many treatment recommendations are extrapolated from adult populations, emphasizing the need to establish the optimal antifungal agent, dosage, and duration of therapy in neonates. Historically, conventional amphotericin B has been considered an efficient and safe treatment approach for most neonatal IFIs. More recently, lipid formulations of amphotericin B have been studied, used alone or in combination with other antifungal agents such as azoles or echinocandins. The aim of this article is to review the published experience in the use of amphotericin B formulations to treat neonatal IFIs.     

A Bayesian Approach to Inferring the Phylogenetic Structure of Communities from Metagenomic Data

Metagenomics provides a powerful new tool set for investigating evolutionary interactions with the environment. However, an absence of model-based statistical methods means that researchers are often not able to make full use of this complex information. We present a Bayesian method for inferring the phylogenetic relationship among related organisms found within metagenomic samples. Our approach exploits variation in the frequency of taxa among samples to simultaneously infer each lineage haplotype, the phylogenetic tree connecting them, and their frequency within each sample. Applications of the algorithm to simulated data show that our method can recover a substantial fraction of the phylogenetic structure even in the presence of high rates of migration among sample sites. We provide examples of the method applied to data from green sulfur bacteria recovered from an Antarctic lake, plastids from mixed Plasmodium falciparum infections, and virulent Neisseria meningitidis samples.     

Trichosporon Infection

Yeast exist throughout nature in association with soil, plants, mammals, and fish. As a result of this continued exposure, all humans are exposed to many different types of yeast through a variety of different routes. Recently, because of the increased population of immunocompromised patients and the extensive use of different antifungals, the incidence of infections due to non-Candida yeast has increased. Of these classic “nonpathogenic” yeast, Trichosporon species have been increasingly described producing deep-seated and disseminated infections that are difficult to predict and diagnose. In addition, the different species of Trichosporon have been found to be less susceptible or resistant to commonly used antifungals. Because of this intrinsic variation in antifungal susceptibility and the fact that these infections are generally seen in severely immunocompromised hosts, they are associated with significant morbidity and mortality, despite their known “nonpathogenic” characteristics described in superficial infections.     

Treatment of Invasive Candida Infections in the Neonatal Intensive Care Unit

Invasive Candida infections are a leading cause of morbidity and mortality in the neonatal intensive care unit (NICU). Extremely preterm and very low birth weight infants are at the highest risk of infection. There are currently no antifungal agents that have FDA-labeling for the treatment of invasive candidiasis in the neonatal population. Based on the current IDSA guidelines, amphotericin and fluconazole are considered first-line options for neonatal candidiasis. The newer antifungal agents (i.e., echinocandins and voriconazole) are currently considered second-line or salvage therapy; however, evidence supporting their use is emerging. This review focuses on the supporting evidence for the selection of antifungal agents for treatment of invasive Candida infections in the NICU.     

Common fragile sites: mechanisms of instability revisited

Common fragile sites (CFSs) are large chromosomal regions prone to breakage upon replication stress that are considered a driving force of oncogenesis. CFSs were long believed to contain sequences blocking fork progression, thus impeding replication completion and leading to DNA breaks upon chromosome condensation. However, recent studies show that delayed completion of DNA replication instead depends on a regional paucity in initiation events. Because the distribution and the timing of these events are cell type dependent, different chromosomal regions can be committed to fragility in different cell types. These new data reveal the epigenetic nature of CFSs and open the way to a reevaluation of the role played by these sites in the formation of chromosome rearrangements found in tumors from different tissues.     

The Scale of Successional Models and Restoration Objectives

Successional models are used to predict how restoration projects will achieve their goals. These models have been developed on different spatial and temporal scales and consequently emphasize different types of dynamics. This paper focuses on the restoration goal of self-sustainability, but only in the context of a long-term goal. Because of the temporal scale of this goal, we must consider the impact of processes arising outside of the restoration site as of greater importance than restoration itself. Because ecological systems are open, restoration sites will be subjected to many external influential processes. Depending on the landscape context, the impact of these processes may not be noticeable, or, at the other extreme, they may prevent the achievement of restoration objectives. A second issue is to emphasize the nature of processes in the long term, that they are a complex of characteristics such as magnitude, frequency, and extent. Ecological systems are only adapted to a range of values in each of these characteristics. Restoration often combines goals that are of different scales. Models appropriate to these goals need consideration.     

Pseudomonas putida and Pseudomonas fluorescens Species Group Recovery from Human Homes Varies Seasonally and by Environment

By shedding light on variation in time as well as in space, long-term biogeographic studies can help us define organisms’ distribution patterns and understand their underlying drivers. Here we examine distributions of Pseudomonas in and around 15 human homes, focusing on the P. putida and P. fluorescens species groups. We describe recovery from 10,941 samples collected during up to 8 visits per home, occurring on average 2.6 times per year. We collected a mean of 141 samples per visit, from sites in most rooms of the house, from the surrounding yards, and from human and pet occupants. We recovered Pseudomonas in 9.7% of samples, with the majority of isolates being from the P. putida and P. fluorescens species groups (approximately 62% and 23% of Pseudomonas samples recovered respectively). Although representatives of both groups were recovered from every season, every house, and every type of environment sampled, recovery was highly variable across houses and samplings. Whereas recovery of P. putida group was higher in summer and fall than in winter and spring, P. fluorescens group isolates were most often recovered in spring. P. putida group recovery from soils was substantially higher than its recovery from all other environment types, while higher P. fluorescens group recovery from soils than from other sites was much less pronounced. Both species groups were recovered from skin and upper respiratory tract samples from healthy humans and pets, although this occurred infrequently. This study indicates that even species that are able to survive under a broad range of conditions can be rare and variable in their distributions in space and in time. For such groups, determining patterns and causes of stochastic and seasonal variability may be more important for understanding the processes driving their biogeography than the identity of the types of environments in which they can be found.     

ALLERGIC IMPLICATIONS OF BLOOD DISORDERS IN INFANCY AND CHILDHOOD

The clinical manifestations of many of the blood disorders are wholly or partially dependent on immunoallergic reactions. A growing body of evidence permits the characterization of antigenantibody mechanisms in connection with hemolytic anemia, purpura and agranulocytosis, and more specifically for each of the blood cell elements and for the vessel wall.These reactions extend to maternal-fetal relationships producing well defined blood disorders manifest at birth or in the neonatal period.Once the effects of the hypersensitive state are set in motion during the course of a blood disorder, therapeutic measures to slow their progress are often futile. Because it is not always possible to identify the potentially allergic child in whom these circumstances will occur, it is extremely important to weigh the advantages of the use of a drug before it is administered especially when its side effects have not yet been thoroughly investigated.Important information has recently been obtained regarding the heightened susceptibility to infection in children with chronic anemia who have had splenectomy to reduce the frequency of transfusions. The hypersensitive responses in children with spleen removed may result in overwhelming and often fulminating infections necessitating rigid criteria in selecting patients of the pediatric age for this operation.     

Neuraminidase inhibitors for treatment of human and avian strain influenza: A comparative modeling study

Treatment of seasonal influenza viral infections using antivirals such as neuraminidase inhibitors (NAIs) has been proven effective if administered within 48 h post-infection. However, there is growing evidence that antiviral treatment of infections with avian-derived strains even as late as 6 days post-infection (dpi) can significantly reduce infection severity and duration. Using a mathematical model of in-host influenza viral infections which can capture the kinetics of both a short-lived, typical, seasonal infection and a severe infection exhibiting sustained viral titer, we explore differences in the effects of NAI treatment on both types of influenza viral infections. Comparison of our model's behavior against experimental data from patients naturally infected with avian strains yields estimates for the times at which patients were infected that are consistent with those reported by the patients, and estimates of drug efficacies that are lower for patients who died than for those who recovered. In addition, our model suggests that the sustained, high, viral titers often seen in more severe influenza virus infections are the reason why antiviral treatment delayed by as much as 6 dpi will still lead to reduced viral titers and shortened illness. We conclude that NAIs may be an effective and beneficial treatment strategy against more severe strains of influenza virus characterized by high, sustained, viral titers. We believe that our mathematical model will be an effective tool in guiding treatment of severe influenza viral infections with antivirals.     

Charred olive stones: experimental and archaeological evidence for recognizing olive processing residues used as fuel

After extracting oil from olives a residue is left usually referred to as the olive oil processing residue (OPR). This study explores the way in which ancient societies may have used OPR as fuel for fires to generate heat and the various issues that are related to the residues of this fuel. After drying, the high heating value and structure of OPR makes it an excellent and efficient fuel. Upgrading OPR further, through thermal conversion or charring, provides an even more efficient fuel (COPR), with a hotter and smoke free flame, a higher heating value and which is lighter in mass and thus easier to transport. After a fire is extinguished two types of remains of the fuel are left i.e. char and ash. Analyses on both remains, recovered from archaeological deposits, could be used as a source of information on fuel utilization. Laboratory experiments on charred modern OPR and stones show that by measuring their reflectance and analyzing their structure under reflected light microscopy, OPR and COPR can be distinguished in the charred material recovered from three archaeological sites in Greece and Syria. Based on these investigations it is suggested that on the three sites COPR was used as fuel. Ash, sampled together with the char, provides the possibility of investigating if other types of fuel were used, apart from OPR or COPR. On the investigated sites no ash was collected, but the analysis of the modern OPR showed that the properties of its ash could be used to distinguish it from other types of fuel. Ash from modern OPR and olive stones showed the presence of phytoliths. The often discussed issue related to the sharpness and smoothness of the edges of charred fragmented olive stones was investigated. The results showed that this is not a reliable criterion for recognizing olive oil production. It is recommended that in addition to the identification of the botanical material more properties of the remains of fuels should be analysed. To prevent destroying and losing char and ash as a result of excavation activities such as flotation and sieving, special measures have to be taken. The results show that analysing char and ash may provide valuable information on the (pyro)technology practised in ancient societies.     

The Microbial Spectrum of Neonatal Sepsis in Uganda: Recovery of Culturable Bacteria in Mother-Infant Pairs

Neonatal sepsis in the developing world is incompletely characterized. We seek to characterize the microbial spectrum involved in sepsis and determine the role of maternal transmission by comparing organisms that can be cultured from septic newborn infants and their mothers. From 80 consecutive mother-infant pairs meeting clinical criteria for neonatal sepsis, we collected infant blood and spinal fluid, and maternal blood and vaginal specimens. Identifiable bacteria were recovered from the blood in 32.5% of infants, and from 2.5% of cerebrospinal fluid cultures, for a total of 35% recoverable putative causative agents. Bacteria recovered from vaginal specimens were not concordant with those recovered from infants. Similarly there was no concordance of bacteria recovered from blood and cerebrospinal fluid. We conclude that relying on traditional bacterial culture techniques does not adequately delineate the role of maternal versus environmental sources of neonatal sepsis in this setting. More sensitive molecular approaches will be needed to properly characterize the maternal and environmental microbial community involved in neonatal sepsis in such developing countries.