Therapeutic effect of antibiotics in the compromised host : an experimental study

The present study was performed in a model of Klebsiella pneumoniae pneumonia and septicemia in rats. This experimental model was used because in leukopenic patients septicemia is a real threat, and K.pneumoniae is one of the pathogens that may be recovered [68, 74, 99, 116, 122, 124]. The experimental design including the infectious disease model is described in chapter 2. The role of the antibiotic dosage schedule as a determinant of therapeutic activity was investigated in relation to various factors such as the severity of infection (chapter 3) , the presence of host defense factors (chapter 4), and the kinetics of antibacterial activity in vitro and in vivo for different classes of antibiotics (chapter 5) . From the three classes of antibiotics, the 8-lactams, the aminoglycosides and the quinolones, ceftazidime, gentamicin and ciprofloxacin were selected as investigational drug, respectively, because of their antibacterial activity against clinically important pathogens and their broad antibacterial spectrum. In addition, the in vitro susceptibility in terms of MBC values of the K.pneumoniae strain used was similar for the three drugs tested, which facilitated a good evaluation of their therapeutic efficacy. The therapeutic effect of ceftazidime, gentamicin and ciprofloxacin in relation to the duration of infection and the bacterial growth rate is described in chapter 6. Finally in chapter 7 the experimental results obtained are discussed with reference to the observations of other investigators. The chapters 3 through 6 represent the appendix papers

Does No-Tillage Mitigate Stover Removal in Irrigated Continuous Corn? A Multi-Location Assessment

No-tillage (NT) may ameliorate negative effects on soil properties from corn (Zea mays L.) stover harvest, but few long-term irrigated continuous corn production systems have been evaluated to test this hypothesis. We evaluated three long-term no-tillage sites (4–13 yr) in Nebraska and Colorado that spanned a range of precipitation and soil organic carbon (SOC) levels. We measured SOC, d13C of SOC, soil microbial biomass (SMB) and composition (i.e., phospholipid fatty acids, PLFAs), and water stable aggregation at all sites under stover retention vs. removal (~60%). Surface SOC stocks (0–30- cm depth) increased across the gradient and were 46.4, 57.4, and 63.1 Mg C ha–1 for Colorado, central Nebraska, and eastern Nebraska, respectively. Overall, residue removal decreased SOC stocks by 6% and soil aggregation by 12% in the 0- to 30-cm depth. The d13C signature of SOC indicated less new surface C storage under residue removal in Colorado, but not at the two Nebraska sites. Residue harvest did not decrease SMB or change soil microbial community structure, suggesting that high plant productivity buffered community composition from stover harvest impacts under NT but stimulated microbial activity levels that led to SOC loss. The high rates of stover removal used in this study decreased SOC stocks and aggregation at all sites compared to residue retained treatments, suggesting that no-tillage alone was not sufficient to maintain erosion protection and soil function

Seasonal switchgrass ecotype contributions to soil organic carbon, deep soil microbial community composition and rhizodeposit uptake during an extreme drought

The importance of rhizodeposit C and associated microbial communities in deep soil C stabilization is relatively unknown. Phenotypic variability in plant root biomass could impact C cycling through belowground plant allocation, rooting architecture, and microbial community abundance and composition. We used a pulse-chase 13C labeling experiment with compound-specific stable-isotope probing to investigate the importance of rhizodeposit C to deep soil microbial biomass under two switchgrass ecotypes (Panicum virgatum L., Kanlow and Summer) with contrasting root morphology. We quantified root phenology, soil microbial biomass (phospholipid fatty acids, PLFA), and microbial rhizodeposit uptake (13C-PLFAs) to 150 cm over one year during a severe drought. The lowland ecotype, Kanlow, had two times more root biomass with a coarser root system compared to the upland ecotype, Summer. Over the drought, Kanlow lost 78% of its root biomass, while Summer lost only 60%. Rhizosphere microbial communities associated with both ecotypes were similar. However, rhizodeposit uptake under Kanlow had a higher relative abundance of gram-negative bacteria (44.1%), and Summer rhizodeposit uptake was primarily in saprotrophic fungi (48.5%). Both microbial community composition and rhizodeposit uptake shifted over the drought into gram-positive communities. Rhizosphere soil C was greater one year later under Kanlow due to turnover of unlabeled structural root C. Despite a much greater root biomass under Kanlow, rhizosphere δ13C was not significantly different between the two ecotypes, suggesting greater microbial C input under the finer rooted species, Summer, whose microbial associations were predominately saprotrophic fungi. Ecotype specific microbial communities can direct rhizodeposit C flow and C accrual deep in the soil profile and illustrate the importance of the microbial community in plant strategies to survive environmental stress such as drought

Low prevalence of non-typable Methicillin-resistant Staphylococcus aureus in meat products in The Netherlands

Recently, a new clone of methicillin resistant Staphylococcus (S.) aureus (MRSA) emerged in the Netherlands that was related to pigfarming. A survey in pigs showed that nearly 40% carried this new clone. This new type is characterised by bemg untypable with pulsed field gel electrophoresis (PFGE). This study was undertaken to determme the prevalence and genetic relationship of S.aureus and MRSA in meal products

Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1

Pontocerebellar hypoplasia (PCH) describes a group of rare heterogeneous neurodegenerative diseases with prenatal onset. Here we describe eight children with PCH from four unrelated families harboring the homozygous MINPP1 (NM_004897.4) variants; c.75_94del, p.(Leu27Argfs*39), c.851 C > A, p.(Ala284Asp), c.1210 C > T, p.(Arg404*), and c.992 T > G, p.(Ile331Ser). The homozygous p.(Leu27Argfs*39) change is predicted to result in a complete absence of MINPP1. The p.(Arg404*) would likely lead to a nonsense mediated decay, or alternatively, a loss of several secondary structure elements impairing protein folding. The missense p.(Ala284Asp) affects a buried, hydrophobic residue within the globular domain. The introduction of aspartic acid is energetically highly unfavorable and therefore predicted to cause a significant reduction in protein stability. The missense p.(Ile331Ser) affects the tight hydrophobic interactions of the isoleucine by the disruption of the polar side chain of serine, destabilizing the structure of MINPP1. The overlap of the above-mentioned genotypes and phenotypes is highly improbable by chance. MINPP1 is the only enzyme that hydrolyses inositol phosphates in the endoplasmic reticulum lumen and several studies support its role in stress induced apoptosis. The pathomechanism explaining the disease mechanism remains unknown, however several others genes of the inositol phosphatase metabolism (e.g., INPP5K, FIG4, INPP5E, ITPR1) are correlated with phenotypes of neurodevelopmental disorders. Taken together, we present MINPP1 as a novel autosomal recessive pontocerebellar hypoplasia gene

Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1.

Pontocerebellar hypoplasia (PCH) describes a group of rare heterogeneous neurodegenerative diseases with prenatal onset. Here we describe eight children with PCH from four unrelated families harboring the homozygous MINPP1 (NM_004897.4) variants; c.75_94del, p.(Leu27Argfs*39), c.851 C > A, p.(Ala284Asp), c.1210 C > T, p.(Arg404*), and c.992 T > G, p.(Ile331Ser). The homozygous p.(Leu27Argfs*39) change is predicted to result in a complete absence of MINPP1. The p.(Arg404*) would likely lead to a nonsense mediated decay, or alternatively, a loss of several secondary structure elements impairing protein folding. The missense p.(Ala284Asp) affects a buried, hydrophobic residue within the globular domain. The introduction of aspartic acid is energetically highly unfavorable and therefore predicted to cause a significant reduction in protein stability. The missense p.(Ile331Ser) affects the tight hydrophobic interactions of the isoleucine by the disruption of the polar side chain of serine, destabilizing the structure of MINPP1. The overlap of the above-mentioned genotypes and phenotypes is highly improbable by chance. MINPP1 is the only enzyme that hydrolyses inositol phosphates in the endoplasmic reticulum lumen and several studies support its role in stress induced apoptosis. The pathomechanism explaining the disease mechanism remains unknown, however several others genes of the inositol phosphatase metabolism (e.g., INPP5K, FIG4, INPP5E, ITPR1) are correlated with phenotypes of neurodevelopmental disorders. Taken together, we present MINPP1 as a novel autosomal recessive pontocerebellar hypoplasia gene

Seasonal switchgrass ecotype contributions to soil organic carbon, deep soil microbial community composition and rhizodeposit uptake during an extreme drought

The importance of rhizodeposit C and associated microbial communities in deep soil C stabilization is relatively unknown. Phenotypic variability in plant root biomass could impact C cycling through belowground plant allocation, rooting architecture, and microbial community abundance and composition. We used a pulse-chase 13C labeling experiment with compound-specific stable-isotope probing to investigate the importance of rhizodeposit C to deep soil microbial biomass under two switchgrass ecotypes (Panicum virgatum L., Kanlow and Summer) with contrasting root morphology. We quantified root phenology, soil microbial biomass (phospholipid fatty acids, PLFA), and microbial rhizodeposit uptake (13C-PLFAs) to 150 cm over one year during a severe drought. The lowland ecotype, Kanlow, had two times more root biomass with a coarser root system compared to the upland ecotype, Summer. Over the drought, Kanlow lost 78% of its root biomass, while Summer lost only 60%. Rhizosphere microbial communities associated with both ecotypes were similar. However, rhizodeposit uptake under Kanlow had a higher relative abundance of gram-negative bacteria (44.1%), and Summer rhizodeposit uptake was primarily in saprotrophic fungi (48.5%). Both microbial community composition and rhizodeposit uptake shifted over the drought into gram-positive communities. Rhizosphere soil C was greater one year later under Kanlow due to turnover of unlabeled structural root C. Despite a much greater root biomass under Kanlow, rhizosphere δ13C was not significantly different between the two ecotypes, suggesting greater microbial C input under the finer rooted species, Summer, whose microbial associations were predominately saprotrophic fungi. Ecotype specific microbial communities can direct rhizodeposit C flow and C accrual deep in the soil profile and illustrate the importance of the microbial community in plant strategies to survive environmental stress such as drought

Gray matter imaging in multiple sclerosis: what have we learned?

At the early onset of the 20th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis (MS). However, as white matter pathology long received predominant attention in this disease, and histological staining techniques for detecting myelin in the gray matter were suboptimal, it was not until the beginning of the 21st century that the true extent and importance of gray matter pathology in MS was finally recognized. Gray matter damage was shown to be frequent and extensive, and more pronounced in the progressive disease phases. Several studies subsequently demonstrated that the histopathology of gray matter lesions differs from that of white matter lesions. Unfortunately, imaging of pathology in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques. However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage in MS has considerably improved. This has important consequences for studying the clinical correlates of gray matter damage. In this review, we provide an overview of what has been learned about imaging of gray matter damage in MS, and offer a brief perspective with regards to future developments in this field