Host-microbe interplay in persistent Staphylococcus aureus nasal carriage in HIV patients

It has been shown that persistent Staphylococcus aureus nasal carriage results in increased bacterial dispersal and a higher risk of infection compared to non-or-intermittent S. aureus carriage. Although many studies investigated S. aureus nasal carriage in HIV patients, none compared persistent carriage to non-persistent carriage nor were studies performed in the HAART era. We investigated the host-microbe interplay of persistent S. aureus nasal carriage in HIV-infected patients by studying host determinants of persistent carriage as well as the genetic structure of S. aureus strains isolated. We compared this genetic structure with the previously determined population structure of S. aureus isolates obtained from healthy individuals. Between February 2004 and June 2005 all HIV patients visiting the outpatient department of Erasmus MC (Rotterdam, The Netherlands) were asked to participate in this study. Participants were interviewed and screened for persistent S. aureus carriage using two semi-quantitative nasal swab cultures. For 443 patients two cultures were available, 131 (29.6%) were persistent carriers, which is significantly higher as compared to healthy individuals from the same geographic region (17.6%; P<0.0001). Male sex (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.32-3.73), current smoking (OR, 0.58; 95% CI, 0.38-0.90), Pneumocystis jiroveci pneumonia (PCP) prophylaxis (OR, 0.39; 95% CI, 0.16-0.97) and antiretroviral therapy (OR, 0.61; 95% CI, 0.38-0.98) were independent determinants of persistent carriage. Only two strains were mecA positive (1.2%) and no PVL positive strains were detected. The population structure of S. aureus strains isolated from HIV patients appeared to be strongly overlapping with that of S. aureus isolates from healthy individuals.     

Nephrotoxicity of halogenated alkenyl cysteine-S-conjugates

In 1916 a relationship was postulated between the occurrence of aplastic anaemia in cattle and the soy bean meal that they had been fed, which had been extracted with trichloroethylene. The toxic compound was later identified as S-(1,2-dichlorovinyl)-L-cysteine (DCV-Cys). In addition to effects on the hemopoietic system it also produced nephrotoxicity in calves. In rats only renal tubular necrosis was found. Further research demonstrated that other halogenated hydrocarbons produced similar nephrotoxicity. The haloalkenyl cysteine-S-conjugates (Cys-S-conjugates) have extensively been studied; this has provided new insight into the biochemical processes that lead to nephrotoxicity. It has been shown that a combination of transport processes and specific metabolic pathways, resulting in reactive intermediates that bind to cellular macromolecules, makes the kidney vulnerable to the noxious effects of the haloalkenyl Cys-S-conjugates. The first part of this review gives a brief overview of the bioactivation of the haloalkenes; in the second part the present knowledge of the underlying mechanisms of cytotoxicity will be outlined.     

Long-Term Health Related Quality of Life following Intensive Care during Treatment for Haematological Malignancies

Objective

Long-term health-related quality of life (HRQoL) was determined for patients admitted to the haematology ward who needed intensive care treatment (H-IC+) and compared with those who did not (H-IC−) as well as with that for patients admitted to the general ICU (nH-IC+).

Methods

A cross-sectional study was carried out median 18 months after admission by employing the short form-36, checklist for individual strength, cognitive failure questionnaire and hospital anxiety and depression scale.

Results

27 (79%) of the 34 H-IC+ patients approached, and 93 (85%) of the 109 H-IC− patients approached replied. Data were adjusted for relevant covariates and matched with those of 149 patients in the general ICU. Apart from the lower role-physical functioning score for H-IC+ (P = 0.04) no other differences were found between H-IC+ and H-IC−. Groups H-IC+ and nH-IC+ evaluated their HRQoL on SF-36 similarly, except for the lower aggregated physical component summary (PCS) for H-IC+ (P<0.0001). After adjusting for PCS, no significant differences in CIS, CFQ and HADS were observed between the groups.

Conclusions

Eighteen months after admission, patients treated for haematological malignancies reported similar HRQoL, whether or not they had received intensive care treatment, but reported a lower PCS than those of patients in the general ICU. Hence, there is no reason to assume that admission to the ICU has a negative impact on long-term HRQoL, so this should not affect the decision whether or not to transfer patients with haematological malignancies to the ICU.     

An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians

Genome-Wide Association studies (GWAS) of both Crohn's Disease (CD) and Ulcerative Colitis (UC) have unearthed over 40 risk conferring variants. Recently, a meta-analysis on UC revealed several loci, most of which were either previously associated with UC or CD susceptibility in populations of European origin. In this study, we attempted to replicate these findings in an ethnically distinct north Indian UC cohort. 648 UC cases and 850 controls were genotyped using Infinium Human 660W-quad. Out of 59 meta-analysis index SNPs, six were not in the SNP array used in the study. Of the remaining 53 SNPs, four were found monomorphic. Association (p<0.05) at 25 SNPs was observed, of which 15 were CD specific. Only five SNPs namely rs2395185 (HLA-DRA), rs3024505 (IL10), rs6426833 (RNF186), rs3763313 (BTNL2) and rs2066843 (NOD2) retained significance after Bonferroni correction. These results (i) reveal limited replication of Caucasian based meta-analysis results; (ii) reiterate overlapping molecular mechanism(s) in UC and CD; (iii) indicate differences in genetic architecture between populations; and (iv) suggest that resources such as HapMap need to be extended to cover diverse ethnic populations. They also suggest a systematic GWAS in this terrain may be insightful for identifying population specific IBD risk conferring loci and thus enable cross-ethnicity fine mapping of disease loci.     

Morphological effects of high dose neomycin sulphate on the small and large intestine

The morphology of the intestinal wall and the activity of certain mucosal enzyme systems in the course of neomycin treatment were evaluated. Conventional and, to study the role of the bacterial flora, germ-free rats received 500 mg neomycin daily by stomach tube. Rats were sacrificed after seven days and small intestine (proximal and distal part) together with segments of the colon were removed and prepared for histochemistry. The colon and proximal small intestine of untreated conventional and germ-free animals did not show appreciable differences in staining activity after treatment with neomycin. Neomycin diminished both in normal and germ-free rats the activity of NAD tetrazolium reductase, succinate dehydrogenase, esterase, alkaline phosphatase and acid phosphatase in the distal small intestine. The findings of this study indicate that explanations for the beneficial effects of neomycin on hyperammonemia in liver disease should not only include the bactericidal action of neomycin but also its influence on absorption and metabolic functions of the mucosal cells.     

Comparison of tuber and shoot formation from in vitro cultured potato explants

The development of axillary buds of potato (Solanum tuberosum L.) plants, cultured in vitro, was analyzed. Depending on the composition of the culture medium, the buds developed into either tubers (medium with 8% sucrose), shoots (1% sucrose), or stolons (8% sucrose and 0.5 μM gibberellin). Endogenous sugar and starch levels, and key-enzymes involved in the conversion of sucrose to starch were determined at different stages of development. Moreover, the spatial distribution of sugar levels and enzyme activities were determined within the developing structures. Glucose and fructose decreased upon tuber formation, most noticeably in the swelling parts, where also starch accumulated. The activities of sucrose synthase, fructokinase and ADP-glucose pyrophosphorylase were highest under tuber-inducing conditions, the increase being confined to the tubers, and absent in the subtending stolons. It is concluded that changes in the measured parameters, observed under tuberizing conditions, are specifically related to the formation of the tuber, and are confined to the swelling part only. This revised version was published online in June 2006 with corrections to the Cover Date.     

The taste of polycose in hamsters

Hamsters show a preference for Polycose, a mixture of starch-derived glucose polymers, that is as strong as their preference for sucrose. However, in the hamster, taste aversions to Polycose may be less easily acquired than taste aversions to sucrose and the qualitative aspects of Polycose are unknown in this species. In order to examine the taste of Polycose in the hamster, we utilized a taste-aversion protocol with two conditioning trials. Animals were trained to avoid one of three different conditioning stimuli: 50 mM sucrose, 100 mM Polycose and a mixture of 50 mM sucrose with 100 mM Polycose. Control animals were conditioned with deionized water. After the second conditioning trial, generalization testing began for the three conditioning stimuli plus 3 mM citric acid, 300 mM KCI and 30 mM NaCl. The results showed that aversions to Polycose, sucrose or the Polycose/sucrose mixture cross- generalized, demonstrating that Polycose and sucrose share a common taste percept in the hamster. None of the aversions generalized to NaCl, citric acid or KCI. In addition, comparisons among the patterns of taste generalizations indicated that the tastes of Polycose and sucrose also had distinct qualitative components. Finally, although the taste of 100 mM Polycose was more salient than the taste of 50 mM sucrose, the taste of sucrose could still be detected in a mixture with Polycose.      

Effect of soil drying on growth,biomass allocation and leaf gas exchange of two annual grass species

Influence of short-term water stress on plant growth and leaf gas exchange was studied simultaneously in a growth chamber experiment using two annual grass species differing in photosynthetic pathway type, plant architecture and phenology:Triticum aestivum L. cv. Katya-A-1 (C₃, a drought resistant wheat cultivar of erect growth) andTragus racemosus (L.) All. (C₄, a prostrate weed of warm semiarid areas). At the leaf level, gas exchange rates declined with decreasing soil water potential for both species in such a way that instantaneous photosynthetic water use efficiency (PWUE, mmol CO₂ assimilated per mol H₂O transpired) increased. At adequate water supply, the C₄ grass showed much lower stomatal conductance and higher PWUE than the C₃ species, but this difference disappeared at severe water stress when leaf gas exchange rates were similarly reduced for both species. However, by using soil water more sparingly, the C₄ species was able to assimilate under non-stressful conditions for a longer time than the C₃ wheat did. At the whole-plant level, decreasing water availability substantially reduced the relative growth rate (RGR) ofT. aestivum, while biomass partitioning changed in favour of root growth, so that the plant could exploit the limiting water resource more efficiently. The change in partitioning preceded the overall reduction of RGR and it was associated with increased biomass allocation to roots and less to leaves, as well as with a decrease in specific leaf area. Water saving byT. racemosus sufficiently postponed water stress effects on plant growth occurring only as a moderate reduction in leaf area enlargement. For unstressed vegetative plants, relative growth rate of the C₄ T. racemosus was only slightly higher than that of the C₃ T. aestivum, though it was achieved at a much lower water cost. The lack of difference in RGR was probably due to growth conditions being relatively suboptimal for the C₄ plant and also to a relatively large investment in stem tissues by the C₄ T. racemosus. Only 10% of the plant biomass was allocated to roots in the C₄ species while this was more than 30% for the C₃ wheat cultivar. These results emphasize the importance of water saving and high WUE of C₄ plants in maintaining growth under moderate water stress in comparison with C₃ species.     

The neurochrome

Recording of simultaneous but separated activity of neural populations overwhelms the experimenter with a large amount of information. A clearly structured display technique the Neurochrome is introduced, usable on-line and real-time. It shows neural activity patterns while preserving neural identity by employing a color code. The Neurochrome assists the experimenter in generating and verifying hypotheses about neural correlations and stimulus-event relations already during the experiment. In auditory research single neurons are characterized by their spectro-temporal sensitivity to auditory stimuli. A straightforward generalization of this concept, applicable to neural populations, is proposed leading to a global indication of a populations' activity to stimuli: the Multi-Unit Spectro-Temporal Sensitivity. This approach is inversely related to the Neurochrome, the latter however containing more information. The combination of both approaches seems quite powerful in the investigation of neural assemblies. The procedures are illustrated with examples of extracellular multiunit recordings from the auditory midbrain of the grassfrog (Rana temporaria L.).     

Development of a competitive immunoassay for the determination of N-(2-hydroxypropyl)valine adducts in human haemoglobin and its application in biological monitoring.

Propylene oxide (PO) is an important industrial compound and a directly acting mutagen. Human exposure to PO can be monitored by the determination of haemoglobin adducts. An immunoassay that quantifies the N-terminal adduct N-(2-hydroxypropyl)valine in whole haemoglobin was developed and its potential usefulness as a tool for biologically monitoring occupational exposure was demonstrated. Analytical reliability was confirmed in a comparative study with GC-MS (range 3.7-992 nmol g-1 haemoglobin (Hb), correlation coefficient 0.99, n=10). The assay has been configured as a competitive enzyme-linked immunosorbent assay to facilitate the rapid throughput of samples. The assay employs a whole blood matrix and has a working range of 2-250 pmol g-1 Hb. It does not appear to be affected by structurally similar metabolites and has been used to determine adducts in human blood samples. The first results in potentially exposed workers indicate the assay's high potential usefulness in routine occupational biomonitoring of exposure to PO.