A comparison of renal phosphorus regulation in thermally-injured and multiple trauma patients receiving specialized nutrition support

To compare phosphorus intake and renal phosphorus regulation between thermally injured patients and multiple trauma patients, 40 consecutive critically ill patients, 20 with thermal injury and 20 with multiple trauma, who required enteral tube feeding were evaluated. Phosphorus intakes were recorded for 14 days from the initiation of tube feeding which was started 1 to 3 days post-injury. Serum for determination of phosphorus concentrations was collected at days 1, 3, 7, and 14 of the study period. A 24-hour urine collection was obtained during the first and second weeks of nutrition support for urinary phosphorus excretion, fractional excretion of phosphorus, renal threshold phosphate concentration, and phosphorus clearance. Average total daily phosphorus intake during the 14-day study for thermally injured patients and multiple trauma patients was 0.99 ± 0.26 mmol/kg/d vs 0.58 ± 0.21 mmol/kg/d, respectively, p \u3c .001. Serum phosphorus concentration on the third day of observation was significantly lower in the thermally injured group than those with multiple trauma (1.9 ± 0.8 mg/dL vs 3.0 ± 0.8 mg/dL, p ≤ .01). A trend toward hypophosphatemia in the thermally injured group persisted by the seventh day of feeding (2.7 ± 1.2 mg/dL vs 3.3 ± 0.6 mg/dL, p ≤ .04). Differences in urinary phosphorus excretion was not statistically significant between the thermally injured and multiple trauma groups (271 ± 213 mg/d vs 171 ± 181 mg/d for week 1, and 320 ± 289 mg/d vs 258 ± 184 mg/d for week 2, respectively). Urinary phosphorus clearance, fractional excretion of phosphorus, or renal threshold phosphate concentrations were also not significantly different between thermally injured and multiple trauma patients. During nutrition support, serum phosphorus concentrations are lower in thermally injured patients compared with multiple trauma patients despite receiving a significantly greater intake of phosphorus. Renal phosphorus regulation does not significantly contribute to the profound hypophosphatemia observed in thermally injured patients when compared with multiple trauma patients during nutrition support

Inositol phosphorylceramide synthase null Leishmania are viable and virulent in animal infections where salvage of host sphingomyelin predominates

Many pathogens synthesize inositol phosphorylceramide (IPC) as the major sphingolipid (SL), differing from the mammalian host where sphingomyelin (SM) or more complex SLs predominate. The divergence between IPC synthase and mammalian SL synthases has prompted interest as a potential drug target. However, in the trypanosomatid protozoan Leishmania, cultured insect stage promastigotes lack de novo SL synthesis (Δspt

Accuracy of predictive methods to estimate resting energy expenditure of thermally-injured patients

Background The purpose of this study was to evaluate the bias and precision of 46 methods published from 1953 to 2000 for estimating resting energy expenditure (REE) of thermally injured patients. Methods Twenty-four adult patients with ≥20% body surface area burn admitted to a burn center who required specialized nutrition support and who had their REE measured via indirect calorimetry (IC) were evaluated. Patients with morbid obesity, human immunovirus, malignancy, pregnancy, hepatic or renal failure, neuromuscular paralysis, or those requiring a FiO2 \u3e50% or positive end expiratory pressure (PEEP) ≥10 cm H2O were excluded. One steady-state measured REE measurement (MEE) was obtained per patient. The methods of Sheiner and Beal were used to assess bias and precision of these methods. The formulas were considered unbiased if the 95% confidence interval (CI) for the error (kilocalories per day) intersected 0 and were considered precise if the 95% CI for the absolute error (%) was within 15% of MEE. Results MEE was 2780 ± 567 kcal/d or 158% ± 34% of the Harris Benedict equations. None of the methods was precise (≤15% CI error). Over one-half (57%) of the 46 methods had a 95% confidence interval error \u3e30% of the MEE. Forty-eight percent of the methods were unbiased, 33% were biased toward overpredicting MEE, and 19% consistently underpredicted MEE. The pre-1980s methods more frequently overpredicted MEE compared with the 1990 to 2000 (p \u3c .01) and 1980 to 1989 (p \u3c .05) published methods, respectively. The most precise unbiased methods for estimating MEE were those of Milner (1994) at a mean error of 16% (CI of 10% to 22%), Zawacki (1970) with a mean error of 16% (CI of 9% to 23%), and Xie (1993) at a mean error of 18% (CI of 12% to 24%). The conventional 1.5 times the Harris Benedict equations was also unbiased and had a mean error of 19% (CI of 9% to 29%). Conclusions Thermally injured patients are variably hypermetabolic and energy expenditure cannot be precisely predicted. If IC is not available, the most precise, unbiased methods were those of Milner (1994), Zawacki (1970), and Xie (1993)

Minimal, superficial DNA damage in human skin from filtered far-ultraviolet C

Funding: This study was funded in part by MR/P012248/1 to R.P.H. from the Medical Research Council.Publisher PDFPeer reviewe

Tilting the balance between RNA interference and replication eradicates Leishmania RNA virus 1 and mitigates the inflammatory response.

Many Leishmania (Viannia) parasites harbor the double-stranded RNA virus Leishmania RNA virus 1 (LRV1), which has been associated with increased disease severity in animal models and humans and with drug treatment failures in humans. Remarkably, LRV1 survives in the presence of an active RNAi pathway, which in many organisms controls RNA viruses. We found significant levels (0.4 to 2.5%) of small RNAs derived from LRV1 in both Leishmania braziliensis and Leishmania guyanensis, mapping across both strands and with properties consistent with Dicer-mediated cleavage of the dsRNA genome. LRV1 lacks cis- or trans-acting RNAi inhibitory activities, suggesting that virus retention must be maintained by a balance between RNAi activity and LRV1 replication. To tilt this balance toward elimination, we targeted LRV1 using long-hairpin/stem-loop constructs similar to those effective against chromosomal genes. LRV1 was completely eliminated, at high efficiency, accompanied by a massive overproduction of LRV1-specific siRNAs, representing as much as 87% of the total. For both L. braziliensis and L. guyanensis, RNAi-derived LRV1-negative lines were no longer able to induce a Toll-like receptor 3-dependent hyperinflammatory cytokine response in infected macrophages. We demonstrate in vitro a role for LRV1 in virulence of L. braziliensis, the Leishmania species responsible for the vast majority of mucocutaneous leishmaniasis cases. These findings establish a targeted method for elimination of LRV1, and potentially of other Leishmania viruses, which will facilitate mechanistic dissection of the role of LRV1-mediated virulence. Moreover, our data establish a third paradigm for RNAi-viral relationships in evolution: one of balance rather than elimination

A Comparative Study of the ReCell® Device and Autologous Spit-Thickness Meshed Skin Graft in the Treatment of Acute Burn Injuries.

Early excision and autografting are standard care for deeper burns. However, donor sites are a source of significant morbidity. To address this, the ReCell® Autologous Cell Harvesting Device (ReCell) was designed for use at the point-of-care to prepare a noncultured, autologous skin cell suspension (ASCS) capable of epidermal regeneration using minimal donor skin. A prospective study was conducted to evaluate the clinical performance of ReCell vs meshed split-thickness skin grafts (STSG, Control) for the treatment of deep partial-thickness burns. Effectiveness measures were assessed to 1 year for both ASCS and Control treatment sites and donor sites, including the incidence of healing, scarring, and pain. At 4 weeks, 98% of the ASCS-treated sites were healed compared with 100% of the Controls. Pain and assessments of scarring at the treatment sites were reported to be similar between groups. Significant differences were observed between ReCell and Control donor sites. The mean ReCell donor area was approximately 40 times smaller than that of the Control (P < .0001), and after 1 week, significantly more ReCell donor sites were healed than Controls (P = .04). Over the first 16 weeks, patients reported significantly less pain at the ReCell donor sites compared with Controls (P ≤ .05 at each time point). Long-term patients reported higher satisfaction with ReCell donor site outcomes compared with the Controls. This study provides evidence that the treatment of deep partial-thickness burns with ASCS results in comparable healing, with significantly reduced donor site size and pain and improved appearance relative to STSG

Sampling strategies for frequency spectrum-based population genomic inference

Background The allele frequency spectrum (AFS) consists of counts of the number of single nucleotide polymorphism (SNP) loci with derived variants present at each given frequency in a sample. Multiple approaches have recently been developed for parameter estimation and calculation of model likelihoods based on the joint AFS from two or more populations. We conducted a simulation study of one of these approaches, implemented in the Python module δaδi, to compare parameter estimation and model selection accuracy given different sample sizes under one- and two-population models. Results Our simulations included a variety of demographic models and two parameterizations that differed in the timing of events (divergence or size change). Using a number of SNPs reasonably obtained through next-generation sequencing approaches (10,000 - 50,000), accurate parameter estimates and model selection were possible for models with more ancient demographic events, even given relatively small numbers of sampled individuals. However, for recent events, larger numbers of individuals were required to achieve accuracy and precision in parameter estimates similar to that seen for models with older divergence or population size changes. We quantify i) the uncertainty in model selection, using tools from information theory, and ii) the accuracy and precision of parameter estimates, using the root mean squared error, as a function of the timing of demographic events, sample sizes used in the analysis, and complexity of the simulated models. Conclusions Here, we illustrate the utility of the genome-wide AFS for estimating demographic history and provide recommendations to guide sampling in population genomics studies that seek to draw inference from the AFS. Our results indicate that larger samples of individuals (and thus larger AFS) provide greater power for model selection and parameter estimation for more recent demographic events. Electronic supplementary material The online version of this article (doi:10.1186/s12862-014-0254-4) contains supplementary material, which is available to authorized users

ABC inference of multi-population divergence with admixture from unphased population genomic data

Rapidly developing sequencing technologies and declining costs have made it possible to collect genome-scale data from population-level samples in nonmodel systems. Inferential tools for historical demography given these data sets are, at present, underdeveloped. In particular, approximate Bayesian computation (ABC) has yet to be widely embraced by researchers generating these data. Here, we demonstrate the promise of ABC for analysis of the large data sets that are now attainable from nonmodel taxa through current genomic sequencing technologies. We develop and test an ABC framework for model selection and parameter estimation, given histories of three-population divergence with admixture. We then explore different sampling regimes to illustrate how sampling more loci, longer loci or more individuals affects the quality of model selection and parameter estimation in this ABC framework. Our results show that inferences improved substantially with increases in the number and/or length of sequenced loci, while less benefit was gained by sampling large numbers of individuals. Optimal sampling strategies given our inferential models included at least 2000 loci, each approximately 2 kb in length, sampled from five diploid individuals per population, although specific strategies are model and question dependent. We tested our ABC approach through simulation-based cross-validations and illustrate its application using previously analysed data from the oak gall wasp, Biorhiza pallida

Position-sensitive detection of ultracold neutrons with an imaging camera and its implications to spectroscopy

Position-sensitive detection of ultracold neutrons (UCNs) is demonstrated using an imaging charge-coupled device (CCD) camera. A spatial resolution less than 15 $\mu$m has been achieved, which is equivalent to an UCN energy resolution below 2 pico-electron-volts through the relation $\delta E = m_0g \delta x$. Here, the symbols $\delta E$, $\delta x$, $m_0$ and $g$ are the energy resolution, the spatial resolution, the neutron rest mass and the gravitational acceleration, respectively. A multilayer surface convertor described previously is used to capture UCNs and then emits visible light for CCD imaging. Particle identification and noise rejection are discussed through the use of light intensity profile analysis. This method allows different types of UCN spectroscopy and other applications.Comment: 12 figures, 28 pages, accepted for publication in NIM