Patterns of recruitment and injury in a heterogeneous airway network model

In respiratory distress, lung airways become flooded with liquid and may collapse due to surface-tension forces acting on air-liquid interfaces, inhibiting gas exchange. This pa- per proposes a mathematical multiscale model for the mechanical ventilation of a network of occluded airways, where air is forced into the network at a fixed tidal volume, allowing investigation of optimal recruitment strategies. The temporal response is derived from mechanistic models of individual airway reopening, incorporating feedback on the airway pressure due to recruitment. The model accounts for stochastic variability in airway di- ameter and stiffness across and between generations. For weak heterogeneity, the network is completely ventilated via one or more avalanches of recruitment (with airways recruited in quick succession), each characterised by a transient decrease in the airway pressure; avalanches become more erratic for airways that are initially more flooded. However, the time taken for complete ventilation of the network increases significantly as the network becomes more heterogeneous, leading to increased stresses on airway walls. The model predicts that the most peripheral airways are most at risk of ventilation-induced damage. A positive-end-expiratory pressure (PEEP) reduces the total recruitment time but at the cost of larger stresses exerted on airway walls

What works for adolescents with borderline personality disorder: Towards a developmentally informed understanding and structured treatment model

The efficacy of treatment of borderline personality disorder in adolescents is an underresearched area. Although increasing research in borderline personality disorder in adolescents has emerged over the last decade there is a paucity of knowledge about how treatment is adequately designed for this group of patients. As a consequence, it is currently difficult to provide evidence-based guidelines and firm recommendations for how to design and implement borderline treatment in adolescence. In this selective review we summarize the most important research findings concerning treatment for adolescents with borderline personality disorder, including a recent mentalisation-based group treatment program. We highlight pivotal developmental obstacles for psychotherapy in adolescence and integrate these into a framework for the understanding and designing of effective treatment of borderline in adolescence

Sea anemones may thrive in a high CO2 world

Increased seawater pCO 2, and in turn 'ocean acidification' (OA), is predicted to profoundly impact marine ecosystem diversity and function this century. Much research has already focussed on calcifying reef-forming corals (Class: Anthozoa) that appear particularly susceptible to OA via reduced net calcification. However, here we show that OA-like conditions can simultaneously enhance the ecological success of non-calcifying anthozoans, which not only play key ecological and biogeochemical roles in present day benthic ecosystems but also represent a model organism should calcifying anthozoans exist as less calcified (soft-bodied) forms in future oceans. Increased growth (abundance and size) of the sea anemone (Anemonia viridis) population was observed along a natural CO 2 gradient at Vulcano, Italy. Both gross photosynthesis (P G) and respiration (R) increased with pCO 2 indicating that the increased growth was, at least in part, fuelled by bottom up (CO 2 stimulation) of metabolism. The increase of P G outweighed that of R and the genetic identity of the symbiotic microalgae (Symbiodinium spp.) remained unchanged (type A19) suggesting proximity to the vent site relieved CO 2 limitation of the anemones' symbiotic microalgal population. Our observations of enhanced productivity with pCO 2, which are consistent with previous reports for some calcifying corals, convey an increase in fitness that may enable non-calcifying anthozoans to thrive in future environments, i.e. higher seawater pCO 2. Understanding how CO 2-enhanced productivity of non- (and less-) calcifying anthozoans applies more widely to tropical ecosystems is a priority where such organisms can dominate benthic ecosystems, in particular following localized anthropogenic stress. © 2012 Blackwell Publishing Ltd

Genetic Variation in the Complete MgPa Operon and Its Repetitive Chromosomal Elements in Clinical Strains of Mycoplasma genitalium

Mycoplasma genitalium has been increasingly recognized as an important microbe not only because of its significant association with human genital tract diseases but also because of its utility as a model for studying the minimum set of genes necessary to sustain life. Despite its small genome, 4.7% of the total genome sequence is devoted to making the MgPa adhesin operon and its nine chromosomal repetitive elements (termed MgPars). The MgPa operon, along with 9 MgPars, is believed to play an important role in pathogenesis of M. genitalium infection and has also served as the main target for development of diagnostic tools. However, genetic variation in the complete MgPa operon and MgPars among clinical strains of M. genitalium has not been addressed. In this study we examined the genetic variation in the complete MgPa operon (approximately 8.5 kb) and full or partial MgPar sequences (0.4–2.6 kb) in 15 geographically diverse strains of M. genitalium. Extensive variation was present in four repeat regions of the MgPa operon (with homology to MgPars) among and within strains while the non-repeat regions (without homology to MgPars) showed low-level variation among strains and no variation within strains. MgPars showed significant variation among strains but were highly homogeneous within strains, supporting gene conversion as the likely recombination mechanism. When applying our sequence data to evaluate published MgPa operon-based diagnostic PCR assays and genotyping systems, we found that 11 of 19 primers contain up to 19 variable nucleotides and that the target for one of two typing systems is located in a hypervariable repeat region, suggesting the likelihood of false results with some of these assays. This study not only provides new insights into the role of the MgPa operon in the pathogenesis of M. genitalium infection but has important implications for the development of diagnostic tools

Effect of a single dose of pregabalin on herpes zoster pain

<p>Abstract</p> <p>Background</p> <p>The effect of pregabalin on acute herpes zoster pain has not been previously evaluated.</p> <p>Methods</p> <p>In a randomized, double-blind, placebo-controlled, two-session crossover study the effect of a single oral dose of pregabalin (150 mg) on pain and allodynia was evaluated in 8 subjects with herpes zoster.</p> <p>Results</p> <p>Over 6 hours of observation, pain decreased by a mean of 33% with pregabalin and 14% with placebo (p < 0.10). Effects on allodynia and SF-MPQ were not significant.</p> <p>Conclusions</p> <p>Compared to an earlier study of gabapentin 900 mg for acute zoster pain and allodynia that followed a nearly identical protocol, pregabalin had a similar effect on pain and was well tolerated, with no difference from placebo on sleepiness. Common side effects of light-headedness, unsteady gait, and slowed thinking were almost identical to that observed in the earlier study of gabapentin. Subject recruitment proved difficult in part due to the widespread off-label use of gabapentin and pregabalin for acute zoster pain in our region of the USA.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00352651">NCT00352651</a></p

CDK-dependent nuclear localization of B-Cyclin Clb1 promotes FEAR activation during meiosis I in budding yeast

Cyclin-dependent kinases (CDK) are master regulators of the cell cycle in eukaryotes. CDK activity is regulated by the presence, post-translational modification and spatial localization of its regulatory subunit cyclin. In budding yeast, the B-cyclin Clb1 is phosphorylated and localizes to the nucleus during meiosis I. However the functional significance of Clb1's phosphorylation and nuclear localization and their mutual dependency is unknown. In this paper, we demonstrate that meiosis-specific phosphorylation of Clb1 requires its import to the nucleus but not vice versa. While Clb1 phosphorylation is dependent on activity of both CDK and polo-like kinase Cdc5, its nuclear localization requires CDK but not Cdc5 activity. Furthermore we show that increased nuclear localization of Clb1 during meiosis enhances activation of FEAR (Cdc Fourteen Early Anaphase Release) pathway. We discuss the significance of our results in relation to regulation of exit from meiosis I

How heel oxygenation changes under pressure

The mechanism of heel pressure ulcers after hip surgery is not entirely understood. The purpose of this one-group, prospective, repeated-measures design study was to examine how the external pressure of the bed surface affects heel skin oxygen tension in adults on the first 3 days after hip surgery. Transcutaneous oxygen sensors were placed on the plantar surface of each foot, close to the heels. Measures were taken on room air and with an oxygen challenge with the heels (1) suspended above the bed surface (preload), (2) on the bed surface for 15 minutes (loading), and (3) again suspended above the bed surface for 15 minutes (unloading). Eighteen hip surgery patients (mean age 58.3±16.1 years) from two hospitals participated. When compared with preload on room air, both loading and unloading on all 3 days resulted in a reduction in heel oxygen tension bilaterally (p\u3c0.001). Heel oxygenation decreased without the anticipated hyperemic response, raising the question of whether this is a sign of increased pressure ulcer risk. Further work is needed to understand why this short period of external pressure results in decreased oxygenation and why oxygen tension does not return to baseline when pressure is removed