RUSI Journal最新文献

Long-term use of paracetamol (at therapeutic doses) can cause the accumulation of endogenous organic pyroglutamate, resulting in metabolic acidosis with an elevated anion gap. This occurs in the presence of malnutrition, infection, antibiotic use, renal failure and pregnancy. Given the prevalence of these risk factors, this condition is thought to be relatively common in a hospitalised population but is probably significantly underdiagnosed. Prompt recognition is essential because the condition is entirely reversible if the causative agents are withdrawn.Here we describe five cases of pyroglutamic acidosis that we have encountered in a tertiary referral hospital. Together they illustrate the common clinical risk factors and the excellent prognosis, once a diagnosis is made. We describe how a rudimentary acid-base analysis (calculation of the anion gap) usually leads to the diagnosis but how a more nuanced approach may be required in the presence of mixed acid-base disorders.

Background: The effect of a subsequent treated shockable rhythm during cardiopulmonary resuscitation on the outcome of children who suffer out-of-hospital cardiac arrest with initial nonshockable rhythm is unclear. We hypothesized that subsequent treated shockable rhythm in children with out-of-hospital cardiac arrest would improve survival with favorable neurological outcomes (Cerebral Performance Category scale 1-2).

Methods and results: From the All-Japan Utstein Registry, we analyzed the records of 12 402 children (aged <18 years) with out-of-hospital cardiac arrest and initial nonshockable rhythms. Patients were divided into 2 cohorts: subsequent treated shockable rhythm (YES; n=239) and subsequent treated shockable rhythm (NO; n=12 163). The rate of 1-month cerebral performance category 1 to 2 in the subsequent treated shockable rhythm (YES) cohort was significantly higher when compared to the subsequent treated shockable rhythm (NO) cohort (4.6% [11 of 239] vs 1.3% [155 of 12 163]; adjusted odds ratio, 2.90; 95% CI, 1.42-5.36; all P<0.001). In the subsequent treated shockable rhythm (YES) cohort, the rate of 1-month cerebral performance category 1 to 2 decreased significantly as time to shock delivery increased (17.7% [3 of 17] for patients with shock-delivery time 0-9 minutes, 7.3% [8 of 109] for 10-19 minutes, and 0% [0 of 109] for 20-59 minutes; P<0.001 [for trend]). Age-stratified outcomes showed no significant differences between the 2 cohorts in the group aged <7 years old: 1.3% versus 1.4%, P=0.62.

Conclusions: In children with out-of-hospital cardiac arrest and initial nonshockable rhythms, subsequent treated shockable rhythm was associated with improved 1-month survival with favorable neurological outcomes. In the cohort of older children (7-17 years), these outcomes worsened as time to shock delivery increased.

ProMOL, a plugin for the PyMOL molecular graphics system, is a structure-based protein function prediction tool. ProMOL includes a set of routines for building motif templates that are used for screening query structures for enzyme active sites. Previously, each motif template was generated manually and required supervision in the optimization of parameters for sensitivity and selectivity. We developed an algorithm and workflow for the automation of motif building and testing routines in ProMOL. The algorithm uses a set of empirically derived parameters for optimization and requires little user intervention. The automated motif generation algorithm was first tested in a performance comparison with a set of manually generated motifs based on identical active sites from the same 112 PDB entries. The two sets of motifs were equally effective in identifying alignments with homologs and in rejecting alignments with unrelated structures. A second set of 296 active site motifs were generated automatically, based on Catalytic Site Atlas entries with literature citations, as an expansion of the library of existing manually generated motif templates. The new motif templates exhibited comparable performance to the existing ones in terms of hit rates against native structures, homologs with the same EC and Pfam designations, and randomly selected unrelated structures with a different EC designation at the first EC digit, as well as in terms of RMSD values obtained from local structural alignments of motifs and query structures. This research is supported by NIH grant GM078077.