Identifying genes associated with invasive disease in S. pneumoniae by applying a machine learning approach to whole genome sequence typing data.

Streptococcus pneumoniae, a normal commensal of the upper respiratory tract, is a major public health concern, responsible for substantial global morbidity and mortality due to pneumonia, meningitis and sepsis. Why some pneumococci invade the bloodstream or CSF (so-called invasive pneumococcal disease; IPD) is uncertain. In this study we identify genes associated with IPD. We transform whole genome sequence (WGS) data into a sequence typing scheme, while avoiding the caveat of using an arbitrary genome as a reference by substituting it with a constructed pangenome. We then employ a random forest machine-learning algorithm on the transformed data, and find 43 genes consistently associated with IPD across three geographically distinct WGS data sets of pneumococcal carriage isolates. Of the genes we identified as associated with IPD, we find 23 genes previously shown to be directly relevant to IPD, as well as 18 uncharacterized genes. We suggest that these uncharacterized genes identified by us are also likely to be relevant for IPD.

[Changes in regional meningeal immunity in local immunomodulating therapy in patients with acute traumatic intracranial hematomas].

A clinicomorphological study of 660 patients with acute traumatic intracranial hematomas has shown that pneummonia develops in 56% of cases, intracranial complications (purulent meningitis) in 14%.Pyoinflammatory complications were 1.5-1.7 times less common in small-sized hematomas, their total rate and the rate of pneumonias was twice higher in left cerebral hemispheric lesion. On the contrary, intracranial complications were twice more common in right cerebral hemispheric lesion. The structural bases of the regional meningeal immunity system were as follows: the pathways of blood and spinal fluid circulation and dural arachnoidal intercellular fluid; cellular cooperation of the meninx and tissue of the brain; the network of lymph vessels of the dura mater encephali and adventitia of large blood vessels and middle and inferior jugular (regional) lymph nodes. Morphodunctional changes in the local meningeal immunity system in patients with hematomas point to the development of secondary immunodeficiency. Inclusion of regional immunotherapy with T-activin into multimodality treatment decreases the incidence of extra- and intracranial pyoinflammatory complications and mortality.

[Changes of glutamate and GABA in cerebrospinal fluid of patients with pneumonia complicated with central nervous system damage].

Glutamate(Glu), gamma-aminobutyric acid(GABA), and malondialdehyde(MDA) in cerebrospinal fluid (CSF) were measured in 18 children with pneumonia complicated with central nervous system(CNS) damage, 14 children with pneumonia without CNS damage, and 7 children with hypocalcemic tetany. The concentration of Glu and MDA and the ratio of Glu/GABA in CSF of pneumonia without CNS damage were significantly higher than the others. The ratio of Glu/GABA in CSF of the children with pneumonia with consciousness obstacle after convulsion was higher than that without consciousness obstacle after convulsion. These results suggest that Glu and free radicals may play a critical role in the CNS damage caused by pneumonia, however GABA may reduce the CNS damage caused by pneumonia.

High-performance liquid chromatography of amino acids in urine and cerebrospinal fluid.

Two different methods for analyzing amino acids by reversed-phase high-performance liquid chromatography (HPLC), both of which can separate D- and L- stereoisomers, have been used for studying the amino acid composition of cerebrospinal fluid (CSF) and urine. One method, by which Dns derivatives of amino acids are separated as mixed chelate complexes with Cu(II) and a single stereoisomer of a second amino acid, was used to analyze CSF. CSF contains ca. 10 mumole/l per amino acid, compared to 100 mumole/l in serum. The high sensitivity of fluorescence detection enabled complete analysis, starting with 50 microliter of fluid. The second method, which uses lower concentrations of both the copper and the second amino acid and detects amino acids by the change in absorbance of the copper complex, was used to measure the urine concentration of the lysine metabolite, pipecolic acid (piperidine-2-carboxylic acid), a secondary amino acid that is difficult to detect by the more usual detection methods. Our procedure involves passing urine through a cation-exchange column, collecting the fraction containing pipecolic acid, and chromatographing it on a reversed-phase HPLC column with a mobile phase containing L-aspartame and Cu(II). To assess the utility of the method, urine samples from a patient given loading doses of D- or L-isomers were analyzed. When either isomer was administered, both D- and L-isomers were detected, but in different proportions. Varying proportions and concentrations of both isomers were also detected in the urines of patients with hyperpipecolatemia from different metabolic abnormalities.

Prostaglandins in cerebrospinal fluid of patients during various infectious diseases.

Concentrations of prostaglandins of the E and F series were estimated by radioimmunoassay in cerebrospinal fluid (CSF) of 30 febrile patients (infants and adults) and of 19 afebrile, adult patients. In CSF of all feverish patients with meningitis, pneumonia, or pyelonephritis, concentrations of prostaglandins of the E series were about twice higher than those of the afebrile subjects. In contrast, concentrations of prostaglandins of the F series remained largely unchanged during fever. In accord with the results of animal experiments prostaglandins of the E series seem to act as mediators of fever during infectious diseases also in man.