Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.

/pdf/gut-flora-metabolism-of-phosphatidylcholine-promotes-437q5mia6l.pdf

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli. In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.

Extended-spectrum beta-lactamases: a clinical update.

https://stacks.cdc.gov/view/cdc/6674/cdc_6674_DS1.pdf

Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HIPAC/SHEA/APIC/IDSA Hand Hygiene Task Force.

Transcription of the c-fos proto-oncogene is greatly increased within minutes of administering purified growth factors to quiescent 3T3 cells. This stimulation is the most rapid transcriptional response to peptide growth factors yet described, and implies a role for c-fos in cell-cycle control. Transformation by c-fos may result from a temporal deregulation of this control.

Stimulation of 3T3 cells induces transcription of the c- fos proto-oncogene

The publication of the third edition of "Cowan and Steel," almost 20 years after the last, is like the return of a very dear, old friend. The beauty is that despite everything that has happened, the friend is at heart just the same-the mission "to help those who have isolated a bacterium (from a "medical" source) and want to identify it". The book begins with five general chapters on classification and nomenclature; culture media (with Frau Hesse still in her rightful place); isolation techniques; characterisation; and identification. I found the relative dismissal of the antibiogram as an aid to identification unsubtle, and would have liked to have more on the perils of over-reliance on kits. I believe, however, that the warning to the medical microbiologists of the future that the "materials and methods (that) are simply to be taken from the refrigerator or shelf as kits" may be a fool's paradise is timely. The essence of the book for the DIY enthusiast is to be found in chapters 6 and 7 in which all the major medical bacteria are considered in the familiar series of first, second, and third stage tables. Of course they are longer than before; there are, for example, now 26 staphylococcal species compared with eight last time. It seemed to me that a potential inconsistency which the authors challenge us to find concerns motility in Enterococcus faecium. On page 26 it is implied that many strains of E faecium are motile. Table 6.3b has Efaecium non-motile (up to 15% possibly motile according to the key to the tables), but E casseliflavus and E gallinarum motile. On page 66 they refer to E faecium "with its five varieties". What are the facts please? The authors continue a tradition of not being afraid to be different. They have not really given up much in relation to Kiebsiella (the little essay on the genus is great fun) and hang on to Acinetobacter iwoffii. Tables 7.5 and 7.6 are masterpieces of active speciation, being not quite up to date. However, they could have been a little more daring with the old Bacteroides genus, and Mobiluncus dosen't fare well. Overall, however, most of the organisms that turn up in a medical laboratory find a home here, even if only among such taxonomic evasions as "A group of difficult organisms". The Appendices are far from incidental and contain a great deal of valuable information on media and stains, characterisation tests and test organisms (all useful ammunition in current European discussions on standardisation), and on information processing. There are three sections on the bacteriological law in relation to taxonomy, and finally a useful glossary. There are almost 50 pages of references. This book is very definitely a must for anyone who calls him or herself a microbiologist, whether clinical, medical, or technological in persuasion. IAN PHILLIPS Quality Management fo: Safety, Environmental Hes No. 141. IPCS. (Pp 112; Sw Health Organization. 1 92-4-157141-1

https://jcp.bmj.com/content/jclinpath/46/10/975.1.full.pdf

Cowan and Steel's Manual for the Identification of Medical Bacteria

Following the ban of all food animal growth-promoting antibiotics by Sweden in 1986, the European Union banned avoparcin in 1997 and bacitracin, spiramycin, tylosin and virginiamycin in 1999. Three years later, the only attributable effect in humans has been a diminution in acquired resistance in enterococci isolated from human faecal carriers. There has been an increase in human infection from vancomycin-resistant enterococci in Europe, probably related to the increased in usage of vancomycin for the treatment of methicillin-resistant staphylococci. The ban of growth promoters has, however, revealed that these agents had important prophylactic activity and their withdrawal is now associated with a deterioration in animal health, including increased diarrhoea, weight loss and mortality due to Escherichia coli and Lawsonia intra- cellularis in early post-weaning pigs, and clostridial necrotic enteritis in broilers. A directly attributable effect of these infections is the increase in usage of therapeutic antibiotics in food animals, including that of tetracycline, aminoglycosides, trimethoprim/sulphonamide, macrolides and lincosamides, all of which are of direct importance in human medicine. The theoretical and political benefit of the widespread ban of growth promoters needs to be more carefully weighed against the increasingly apparent adverse conse- quences.

/pdf/the-european-ban-on-growth-promoting-antibiotics-and-1or41u9os5.pdf

The European ban on growth-promoting antibiotics and emerging consequences for human and animal health

In this update we provide a list of the 71 P450 genes and the four P450 pseudogenes that have been characterized as of September 30, 1988. The chromosomal locations of many of these genes are also summarized. A modest revision of the initially proposed nomenclature of the P450 superfamily (Nebert et al., DNA 6, 1–11, 1987) is described specifically for the human and mouse chromosomal loci. The motivation for this revision is to conform to the rules of nomenclature for human and mouse genes. Recommendations for the naming of chromosomal loci include the root symbol "CYP" for human ("Cyp" for mouse), denoting "cytochrome P450." We recommend that this root also be used for other organisms. For a chromosomal locus, the root symbol is followed by an Arabic numeral designating the P450 family, a letter indicating the sub-family, and an Arabic numeral representing the individual gene within the family or subfamily. Numbers of the individual genes usually will be assigned in the order the genes are ident...

The P450 Superfamily: Updated Listing of All Genes and Recommended Nomenclature for the Chromosomal Loci

Seventeen per cent of the staff of an intensive care ward were found to have Klebsiella spp contaminating their hands, and these strains could be related to serotypes infecting or colonising patients in the ward on the same day. We identified some simple ward procedures that resulted in contamination of nurses' hands with 100-1000 klebsiellae per hand. Klebsiellae survived on artifically inoculated hands for up to 150 minutes. Handwashing with chlorhexidine hand cleanser reliably gave 98-100% reduction in hand counts, and the introduction of routine handwashing by staff before moving from one patient to the next was associated with a significant and sustained reduction in the number of patients colonised or infected with Klebsiella spp. Staff clothing was occasionally contaminated, but ward air and dust rarely contained klebsiellae.

https://www.bmj.com/content/bmj/2/6098/1315.full.pdf

Ian Phillips

Papers

Cowan and Steel's Manual for the Identification of Medical Bacteria

The European ban on growth-promoting antibiotics and emerging consequences for human and animal health

The P450 Superfamily: Updated Listing of All Genes and Recommended Nomenclature for the Chromosomal Loci

Hands as route of transmission for Klebsiella species.

Beta-lactamase-producing, penicillin-resistant gonococcus.