Circulating brain injury biomarkers increase after endoscopic surgery for pituitary tumors

Pituitary tumors and subsequent treatment with endoscopic transsphenoidal surgery (ETSS) may cause injury to suprasellar structures, causing long-term fatigue and neurocognitive impairment. A method to quantify brain injury after ETSS is not available. In this prospective, exploratory study of patients undergoing ETSS for pituitary tumors, a novel approach to detect possible neuronal damage is presented. Plasma concentrations of brain injury biomarkers (glial fibrillary acidic protein [GFAP], tau, and neurofilament light [NFL]) were measured the day before surgery, immediately after surgery, at day 1 and 5, and at 6 and 12 months after surgery, using enzyme-linked immunosorbent assays. The association between the increase of biomarkers with preoperative tumor extension and postoperative patient-perceived fatigue was evaluated. Suprasellar tumor extension was assessed from MRI scans, and self-perceived fatigue was assessed using the Multidimensional Fatigue Inventory before and 6 months after surgery. Thirty-five patients were included in the analysis. Compared to baseline, GFAP showed a maximal increase at day 1 after surgery (p = 0.0005), tau peaked postoperatively on the day of surgery (p = 0.019), and NFL reached its maximum at day 5 after surgery (p < 0.0001). The increase in GFAP correlated with preoperative chiasmal compression (p = 0.020). The increase in tau was correlated with preoperative chiasmal (p = 0.011) and hypothalamus compression (p = 0.016), and fatigue score 6 months after surgery (p = 0.016). In conclusion, the concentrations of brain injury biomarkers in blood increased after ETSS for pituitary tumors. The results indicate that postoperative plasma GFAP and tau might reflect astroglial and neuronal damage after ETSS

Sex Differences in Sand Lizard Telomere Inheritance: Paternal Epigenetic Effects Increases Telomere Heritability and Offspring Survival

To date, the only estimate of the heritability of telomere length in wild populations comes from humans. Thus, there is a need for analysis of natural populations with respect to how telomeres evolve.Here, we show that telomere length is heritable in free-ranging sand lizards, Lacerta agilis. More importantly, heritability estimates analysed within, and contrasted between, the sexes are markedly different; son-sire heritability is much higher relative to daughter-dam heritability. We assess the effect of paternal age on Telomere Length (TL) and show that in this species, paternal age at conception is the best predictor of TL in sons. Neither paternal age per se at blood sampling for telomere screening, nor corresponding age in sons impact TL in sons. Processes maintaining telomere length are also associated with negative fitness effects, most notably by increasing the risk of cancer and show variation across different categories of individuals (e.g. males vs. females). We therefore tested whether TL influences offspring survival in their first year of life. Indeed such effects were present and independent of sex-biased offspring mortality and offspring malformations.TL show differences in sex-specific heritability with implications for differences between the sexes with respect to ongoing telomere selection. Paternal age influences the length of telomeres in sons and longer telomeres enhance offspring survival

Stroke genetics: prospects for personalized medicine.

Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al

Epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in Sweden 2000–2003, increasing incidence and regional differences

BACKGROUND: The occurrence of methicillin-resistant Staphylococcus aureus (MRSA) has gradually become more frequent in most countries of the world. Sweden has remained one of few exceptions to the high occurrence of MRSA in many other countries. During the late 1990s, Sweden experienced a large health-care associated outbreak which with resolute efforts was overcome. Subsequently, MRSA was made a notifiable diagnosis in Sweden in 2000. METHODS: From the start of being a notifiable disease in January 2000, the Swedish Institute for Infectious Disease Control (SMI) initiated an active surveillance of MRSA. RESULTS: The number of reported MRSA-cases in Sweden increased from 325 cases in 2000 to 544 in 2003, corresponding to an overall increase in incidence from 3.7 to 6.1 per 100000 inhabitants. Twenty five per cent of the cases were infected abroad. The domestic cases were predominantly found through cultures taken on clinical indication and the cases infected abroad through screening. There were considerable regional differences in MRSA-incidence and age-distribution of cases. CONCLUSION: The MRSA incidence in Sweden increased over the years 2000–2003. Sweden now poises on the rim of the same development that was seen in the United Kingdom some ten years ago. A quarter of the cases were infected abroad, reflecting that international transmission is now increasingly important in a low-endemic setting. To remain in this favourable situation, stepped up measures will be needed, to identify imported cases, to control domestic outbreaks and to prevent transmission within the health-care sector

Heritability of telomere variation: it’s all about the environment!

Individual differences in telomere length have been linked to survival and ageing. Understanding the heritability of telomere length can provide important insight into individual differences and facilitate our understanding of the evolution of telomeres. However to gain accurate and meaningful estimates of telomere heritability it is vital that the impact of the environment, and how thismay vary, is understood and accounted for. The aim of this review is to raise awareness of this important, but much under-appreciated point.We outline the factors known to impact telomere length and discuss the fact that telomere length is a trait that changes with age. We highlight statistical methods that can separate genetic from environmental effects and control for confounding variables. We then reviewhowwell previous studies in natural vertebrate populations have taken these factors into account. We argue that studies to date either use methodological techniques that confound environmental and genetic effects, or use appropriate methods but lack sufficient power to fully separate these components.We discuss potential solutions.We conclude that we need larger studies, which also span longer time periods, to account for changing environmental effects, if we are to determine meaningful estimates of the genetic component of telomere length. This article is part of the theme issue ‘Understanding diversity in telomere dynamics'

A principal factor analysis to characterize agricultural exposures among Nebraska veterans

Agricultural workers are at an increased risk of developing chronic respiratory disorders. Accurate estimation of long-term agricultural exposures based on questionnaires has been used to improve the validity of epidemiologic investigations and subsequent evaluation of the association between agricultural exposures and chronic diseases. Our aim was to use principal factor analysis (PFA) to distill exposure data into essential variables characterizing long-term agricultural exposures. This is a crosssectional study of veterans between the ages of 40 and 80 years and who worked on a farm for ≥ 2 years. Participant characteristics were: 98.1% were white males with a mean age 65 ± 8 (SD) years and 39.8% had chronic obstructive pulmonary disease. The final model included four factors and explained 16.6% of the variance in the exposure data. Factor 1 was a heterogeneous factor; however, Factor 2 was exclusively composed of exposure to livestock such as hogs, dairy and poultry. Factor 3 included exposures from jobs on or off the farm such as wood dust, mineral dust, asbestos and spray paint. Crop exposure loaded exclusively in Factor 4 and included lifetime hours of exposure and maximum number of acres farmed in the participants’ lifetime. The factors in the final model were interpretable and consistent with farming practices

Fixed and flexible: coexistence of obligate and facultative migratory strategies in a freshwater fish

Migration is an important event in many animal life histories, but the degree to which individual animals participate in seasonal migrations often varies within populations. The powerful ecological and evolutionary consequences of such partial migration are now well documented, but the underlying mechanisms are still heavily debated. One potential mechanism of partial migration is between-individual variation in body condition, where animals in poor condition cannot pay the costs of migration and hence adopt a resident strategy. However, underlying intrinsic traits may overrule such environmental influence, dictating individual consistency in migratory patterns. Unfortunately, field tests of individual consistency compared to the importance of individual condition on migratory propensity are rare. Here we analyse 6 years of field data on roach migration, gathered by tagging almost 3000 individual fish and monitoring their seasonal migrations over extended periods of time. Our aims were to provide a field test of the role of condition in wild fish for migratory decisions, and also to assess individual consistency in migratory tendency. Our analyses reveal that (1) migratory strategy, in terms of migration/residency, is highly consistent within individuals over time and (2) there is a positive relationship between condition and the probability of migration, but only in individuals that adopt a migratory strategy at some point during their lives. However, life-long residents do not differ in condition to migrants, hence body condition is only a good predictor of migratory tendency in fish with migratory phenotypes and not a more general determinant of migratory tendency for the population. As resident individuals can achieve very high body condition and still remain resident, we suggest that our data provides some of the first field evidence to show that both facultative and obligate strategies can co-exist within populations of migratory animals