Vitamin D and insulin resistance

Vitamin D is a steroid hormone, which in active form binds to the vitamin D receptor. Expression of the vitamin D receptor in diverse cell types (pancreatic islet cells, myocytes, hepatocytes and adipocytes) raises the suspicion that vitamin D may be involved in multiple cellular processes, including the response to insulin. Insulin resistance is a characteristic feature of type 2 DM, and its attenuation may reduce the incidence of type 2 DM and cardiovascular disease. In observational studies, low serum 25-hydroxyvitamin D (25-OHD) concentrations are associated with an increased risk of type 2 DM. It has been suggested that increasing serum 25-OHD concentrations may have beneficial effects on glucose and insulin homeostasis. However, cross-sectional and interventional studies of vitamin D supplementation provide conflicting results and demonstrate no clear beneficial effect of vitamin D on insulin resistance. These studies are complicated by inclusion of different patient cohorts, different 25-OHD assays and different doses and preparations of vitamin D. Any possible association may be confounded by alterations in PTH, 1,25-dihydroxyvitamin D or tissue vitamin D concentrations. We identified 39 studies via MEDLINE and PUBMED. We review the evidence from 10 studies (seven observational and three interventional) examining vitamin D and type 2 DM incidence, and 29 studies (one prospective observational, 12 cross-sectional and 16 interventional trials) examining vitamin D and insulin resistance. Based on this data, it is not possible to state that vitamin D supplementation has any effect on type 2 DM incidence or on insulin resistance. Data from the multiple ongoing randomized controlled trials of vitamin D supplementation due to report over the next few years should help to clarify this area.

Personalized cancer medicine: molecular diagnostics, predictive biomarkers, and drug resistance.

The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution.

The Great Transition:Climate, disease and society in the late-medieval world

In the fourteenth century the Old World witnessed a series of profound and abrupt changes in the trajectory of long-established historical trends. Trans-continental networks of exchange fractured and an era of economic contraction and demographic decline dawned from which Latin Christendom would not begin to emerge until its voyages of discovery at the end of the fifteenth century. In a major new study of this 'Great Transition', assessment is made of the contributions of commercial recession, war, climate change,and eruption of the Black Death to a far-reaching reversal of fortunes which spared no part of Eurasia. A wealth of new historical, palaeoecological and biological evidence are synthesised, including estimates of national income, reconstructions of past climates. and genetic analysis of DNA extracted from the teeth of plague victims, to provide a fresh account of the creation, collapse and realignment of western Europe's late-medieval commercial economy.

Effect of habitat fragmentation on levels and patterns of genetic diversity in natural populations of the peat moss Polytrichum commune

Peat bogs represent unique ecosystems that are under particular threat from fragmentation due to peat harvesting, with only 38% of the original peatland in Europe remaining intact and unaffected by peat cutting, drainage and silviculture. In this study, we have used microsatellite markers to determine levels and patterns of genetic diversity in both cut and uncut natural populations of the peat moss Polytrichum commune. Overall diversity levels suggest that there is more genetic variation present than had previously been assumed for bryophytes. Despite this, diversity values from completely cut bogs were found to be lower than those from uncut peatlands (average 0.729 versus 0.880). In addition, the genetic diversity was more highly structured in the cut populations, further suggesting that genetic drift is already affecting genetic diversity in peat bogs subjected to fragmentation.

Chromosomal rearrangements affecting biofilm production and antibiotic resistance in a Staphylococcus epidermidis strain causing shunt-associated ventriculitis.

Ziebuhr W, Dietrich K, Trautmann M, Wilhelm M. Institut für Molekulare Infektionsbiologie, Würzburg, Germany. w.ziebuhr@mail.uni-wuerzburg.de During two clinical courses of shunt-associated meningitis in a 3-month-old child, five multiresistant S. epidermidis isolates were obtained and analyzed with regard to biofilm production and antibiotic susceptibility. Three S. epidermidis strains, which were initially isolated from the cerebrospinal fluid, produced biofilms on polystyrene tissue culture plates. Following antibiotic treatment and subsequent exchange of the shunt system, sterilization of the CSF was achieved. However, after three weeks a relapse of the infection occurred. The two S. epidermidis isolates obtained now were biofilm negative, but showed an identical resistance pattern as those from the previous infection, except that resistance to rifampicin and increased mininal inhibitory concentrations of aminoglycoside antibiotics had emerged. DNA fingerprinting by PFGE indicated the clonal origin of all isolates. However, some DNA rearrangements and differences in the IS256-specific hybridization patterns could be identified in the isolates from the second infection period that led to altered biofilm formation and increased expression of aminoglycoside resistance traits. The data evidence that variation of biofilm expression occurs in vivo during an infection and highlight the extraordinary genome flexibility of pathogenic S. epidermidis.