A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline.

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.

Pom1 gradient buffering through intermolecular auto-phosphorylation.

Concentration gradients provide spatial information for tissue patterning and cell organization, and their robustness under natural fluctuations is an evolutionary advantage. In rod-shaped Schizosaccharomyces pombe cells, the DYRK-family kinase Pom1 gradients control cell division timing and placement. Upon dephosphorylation by a Tea4-phosphatase complex, Pom1 associates with the plasma membrane at cell poles, where it diffuses and detaches upon auto-phosphorylation. Here, we demonstrate that Pom1 auto-phosphorylates intermolecularly, both in vitro and in vivo, which confers robustness to the gradient. Quantitative imaging reveals this robustness through two system's properties: The Pom1 gradient amplitude is inversely correlated with its decay length and is buffered against fluctuations in Tea4 levels. A theoretical model of Pom1 gradient formation through intermolecular auto-phosphorylation predicts both properties qualitatively and quantitatively. This provides a telling example where gradient robustness through super-linear decay, a principle hypothesized a decade ago, is achieved through autocatalysis. Concentration-dependent autocatalysis may be a widely used simple feedback to buffer biological activities.

Obese, smoker, and obese smoker : is there a general lifestyle gradient?

Aim: Obesity and smoking are major CVD risk factors and may be associated with other unfavourable lifestyle behaviours. Our aim was to investigate the significance of obesity, heavy smoking, and both combined in terms of prevalence trends and their relationship with other lifestyle factors. Methods: We used data from the population-based cross-sectional Swiss Health Survey (5 waves, 1992-2012) comprising 85,575 individuals aged 18 years. Height, weight, and smoking status were self-reported. We used multinomial logistic regression to analyse differences in lifestyle for the combinations of BMI category and smoking status, focusing on obese and heavy smokers. We defined normal-weight never smokers as reference.

Dispersal is a major driver of the latitudinal diversity gradient of Carnivora

AimUnderstanding the relative contribution of diversification rates (speciation and extinction) and dispersal in the formation of the latitudinal diversity gradient - the decrease in species richness with increasing latitude - is a main goal of biogeography. The mammalian order Carnivora, which comprises 286 species, displays the traditional latitudinal diversity gradient seen in almost all mammalian orders. Yet the processes driving high species richness in the tropics may be fundamentally different in this group from that in other mammalian groups. Indeed, a recent study suggested that in Carnivora, unlike in all other major mammalian orders, net diversification rates are not higher in the tropics than in temperate regions. Our goal was thus to understand the reasons why there are more species of Carnivora in the tropics. LocationWorld-wide. MethodsWe reconstructed the biogeographical history of Carnivora using a time-calibrated phylogeny of the clade comprising all terrestrial species and dispersal-extinction-cladogenesis models. We also analysed a fossil dataset of carnivoran genera to examine how the latitudinal distribution of Carnivora varied through time. ResultsOur biogeographical analyses suggest that Carnivora originated in the East Palaearctic (i.e. Central Asia, China) in the early Palaeogene. Multiple independent lineages dispersed to low latitudes following three main paths: toward Africa, toward India/Southeast Asia and toward South America via the Bering Strait. These dispersal events were probably associated with local extinctions at high latitudes. Fossil data corroborate a high-latitude origin of the group, followed by late dispersal events toward lower latitudes in the Neogene. Main conclusionsUnlike most other mammalian orders, which originated and diversified at low latitudes and dispersed out of the tropics', Carnivora originated at high latitudes, and subsequently dispersed southward. Our study provides an example of combining phylogenetic and fossil data to understand the generation and maintenance of global-scale geographical variations in species richness.