Abstract Objective To evaluate the usefulness of the leukocyte (WBC) and neutrophil (ANC) counts, the values of C-reactive protein (CRP), procalcitonin (PCT) and calprotectin (CP) and the APPY1 Test ...panel of biomarkers, to identify children with abdominal pain at low risk of appendicitis. Method Children 2-14 years of age with abdominal pain suggesting AA were prospectively included. PCT, CP, CRP, WBC, ANC and the new plasma APPY1 Test were performed. The final diagnosis was determined by histopathology in cases of AA and telephone follow-up in children discharged without AA. Results Between February 2012 and June 2013, 185 children were enrolled with an average age of 9.32 ± 2.7 years. Eighty-nine (48.1%) were finally diagnosed with AA. The APPY1 Test panel showed the highest discriminatory power, sensitivity 97.8 (95% CI 92.2 to 99.4), negative predictive value (NPV) 95.1 (95% CI 83.9 to 98.7), negative likelihood ratio (LR) 0.06 (95% CI 0.01 to 0.22) and specificity 40.6 (95% CI 31.3 to 50.5). A negative APPY1Test and ANC < 7500/ml, provided a sensitivity of 100 (95% CI 95.9 to 100), NPV 100 (95% CI 89.8 to 100) and specificity 35.4 (95% CI 26.6 to 45.4). In the multivariate analysis, only the APPY1Test and ANC > 7500/ml, were significant risk factors for AA (OR 13.76, 95% CI 3.02 to 62.57 and OR 6.37, 95% 2.89 to 14.28, respectively). Conclusions The APPY1 Test panel with ANC could be useful in identifying children with abdominal pain suggestive of AA who are at low risk of this disease.
The evolution of the Torcas cave system (Sierra de Atapuerca) is analysed in order to shed light on the formation of the Atapuerca archaeological sites and human occupation in the area, critical for ...identifying the paths of the first human dispersal into Europe. The geomorphological analysis of the endokarst system and the regional base levels has revealed a multilevel cave system, with drainage directions from south to north, where old karst springs fed the Pico River. Using morphological and topographic evidence we have correlated the fluvial terraces situated at relative heights of +84–80m and +78–70m above the Arlanzón River (main course), with the first and second cave levels, respectively, both of Early Pleistocene age. The fluvial levels T4 (+60–67m) and T5 (+50–54m) are linked with the third level (Early–Middle Pleistocene), which contains fluvial deposits probably related to terrace T6 (+44–46m). Progressive fluvial incision allowed humans to gain access to the cave system through several entrances from ~1.22Myr until the end of the Middle Pleistocene, when these cave entrances became filled, forming the most interesting hominid-bearing deposits in Europe.
► The Sierra de Atapuerca contains a karst with an impressive archaeological record. ► We have studied the karst system carrying out detailed geomorphological maps. ► The endokarst system is characterised by three paragenetic levels. ► We have related this multilevel system with Pleistocene fluvial base levels.
Pseudomonas aeruginosa produces the peptide siderophore pyoverdine, which is used to acquire essential Fe3+ ions from the environment. PvdQ, an Ntn hydrolase, is required for the biosynthesis of ...pyoverdine. PvdQ knockout strains are not infectious in model systems, suggesting that disruption of siderophore production via PvdQ inhibition could be exploited as a target for novel antibacterial agents, by preventing cells from acquiring iron in the low iron environments of most biological settings. We have previously described a high-throughput screen to identify inhibitors of PvdQ that identified inhibitors with IC50 values of ∼100 μM. Here, we describe the discovery of ML318, a biaryl nitrile inhibitor of PvdQ acylase. ML318 inhibits PvdQ in vitro (IC50 = 20 nM) by binding in the acyl-binding site, as confirmed by the X-ray crystal structure of PvdQ bound to ML318. Additionally, the PvdQ inhibitor is active in a whole cell assay, preventing pyoverdine production and limiting the growth of P. aeruginosa under iron-limiting conditions.
Nasal obstruction (NO) is defined as the subjective perception of discomfort or difficulty in the passage of air through the nostrils. It is a common reason for consultation in primary and ...specialized care and may affect up to 30%-40% of the population. It affects quality of life (especially sleep) and lowers work efficiency. The aim of this document is to agree on how to treat NO, establish a methodology for evaluating and diagnosing it, and define an individualized approach to its treatment. NO can be unilateral or bilateral, intermittent or persistent and may be caused by local or systemic factors, which may be anatomical, inflammatory, neurological, hormonal, functional, environmental, or pharmacological in origin. Directed study of the medical history and physical examination are key for diagnosing the specific cause. NO may be evaluated using subjective assessment tools (visual analog scale, symptom score, standardized questionnaires) or by objective estimation (active anterior rhinomanometry, acoustic rhinometry, peak nasal inspiratory flow). Although there is little correlation between the results, they may be considered complementary and not exclusive. Assessing the impact on quality of life through questionnaires standardized according to the underlying disease is also advisable. NO is treated according to its cause. Treatment is fundamentally pharmacological (topical and/or systemic) when the etiology is inflammatory or functional. Surgery may be necessary when medical treatment fails to complement or improve medical treatment or when other therapeutic approaches are not possible. Combinations of surgical techniques and medical treatment may be necessary.
Summary
Background
Lactate is an already recognized biomarker for short-term mortality in emergency medical services (EMS). However, how different levels of lactate are associated with short-, mid- ...and long-term outcomes should be unveiled.
Aim
To determine how different categories of hyperlactatemia are associated with mortality. We also aim to clinically characterize hyperlactatemia groups.
Design
A multicenter, prospective, observational study performed between January 2019 and February 2022, considering 48 basic life support units and 5 advanced life support units referring to 4 tertiary care hospitals (Spain). Patients were recruited from phone requests for emergency assistance in adults, evacuated to emergency departments. The primary outcome was in-hospital mortality from any cause within the first to the 365-day period following EMS attendance. The main measures were demographical and biochemical variables, prehospital advanced life support techniques used and patient condition categorized in 24 diseases.
Methods
Univariate and Cox regression analysis.
Results
A total of 5072 participants fulfilled inclusion criteria. Group #1 (non-hyperlactatemia) was composed of 2389 subjects (47.1%), Group #2 (mild hyperlactatemia) of 1834 (36.1%), Group #3 (hyperlactatemia) of 333 (6.6%) and, finally, Group #4 (severe hyperlactatemia) of 516 (10.2%). The 1-day mortality was 0.2%, 1.1%, 9% and 22.3% in the four lactate groups, respectively. Long-term mortality (365 days) was 10.2%, 22.7%, 38.7% and 46.7% in the four lactate groups, respectively. Differences between patients’ conditions of lactatemia groups were also found.
Conclusions
Our results demonstrated that prehospital lactate categories were associated with short- and long-term outcomes in a different manner. These results will allow EMS to establish different risk states according to the prehospital lactate categories.
A high-throughput screen (HTS) with the National Institute of Health–Molecular Libraries Small Molecule Repository (NIH–MLSMR) compound collection identified a class of acyl hydrazones to be ...selectively lethal to breast cancer stem cell (CSC) enriched populations. Medicinal chemistry efforts were undertaken to optimize potency and selectivity of this class of compounds. The optimized compound was declared as a probe (ML239) with the NIH Molecular Libraries Program and displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control line (HMLE_sh_GFP).
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