The severity of Puumala hantavirus induced nephropathia epidemica can be better evaluated using plasma interleukin-6 than C-reactive protein determinations

<p>Abstract</p> <p>Background</p> <p>Nephropathia epidemica (NE) is a Scandinavian type of hemorrhagic fever with renal syndrome caused by Puumala hantavirus. The clinical course of the disease varies greatly in severity. The aim of the present study was to evaluate whether plasma C-reactive protein (CRP) and interleukin (IL)-6 levels associate with the severity of NE.</p> <p>Methods</p> <p>A prospectively collected cohort of 118 consecutive hospital-treated patients with acute serologically confirmed NE was examined. Plasma IL-6, CRP, and creatinine, as well as blood cell count and daily urinary protein excretion were measured on three consecutive days after admission. Plasma IL-6 and CRP levels higher than the median were considered high.</p> <p>Results</p> <p>We found that high IL-6 associated with most variables reflecting the severity of the disease. When compared to patients with low IL-6, patients with high IL-6 had higher maximum blood leukocyte count (11.9 <it>vs </it>9.0 × 10⁹/l, <it>P </it>= 0.001) and urinary protein excretion (2.51 <it>vs </it>1.68 g/day, <it>P </it>= 0.017), as well as a lower minimum blood platelet count (55 <it>vs </it>80 × 10⁹/l, <it>P </it>< 0.001), hematocrit (0.34 <it>vs </it>0.38, <it>P </it>= 0.001), and urinary output (1040 <it>vs </it>2180 ml/day, <it>P </it>< 0.001). They also stayed longer in hospital than patients with low IL-6 (8 <it>vs </it>6 days, <it>P </it>< 0.001). In contrast, high CRP did not associate with severe disease.</p> <p>Conclusions</p> <p>High plasma IL-6 concentrations associate with a clinically severe acute Puumala hantavirus infection, whereas high plasma CRP as such does not reflect the severity of the disease.</p

Clinico-pathological and biomolecular findings in Italian patients with multiple cutaneous neurofibromas

<p>Abstract</p> <p>Background</p> <p>Neurofibroma occurs as isolated or multiple lesions frequently associated with neurofibromatosis type 1 (NF1), a common autosomal dominant disorder affecting 1 in 3500 individuals. It is caused by mutations in the <it>NF1 </it>gene, which comprises 60 exons and is located on chromosome 17q11.2. <it>NF1 </it>is a fully penetrant gene exhibiting a mutation rate some 10-fold higher compared with most other disease genes. As a consequence, a high number of cases (up to 50%) are sporadic. Mutation detection is complex due to the large size of the <it>NF1 </it>gene, the presence of pseudogenes and the great variety of lesions.</p> <p>Methods</p> <p>110 patients with at least two neurofibroma lesions recorded in the files of the Pathology Department of the University of Modena during the period 1999-2010, were included in this study. Through interviews and examination of clinical charts, pedigrees were drawn for all patients who were affected by at least two neurofibromas. We attempted to delineate the clinical features of NF1 and the mutational spectrum in the cohort of 11 NF1 families identified. For each proband, the whole coding sequence and all splice sites were studied for mutations, either by the protein truncation test (PTT), or, more frequently, by denaturing high performance liquid chromatography (DHPLC). Two GIST tumors of NF1 patients were tested for somatic NF1 mutations.</p> <p>Results</p> <p>NF1 germline mutations were identified in 7 (68%) patients. A novel mutation, c.3457_3460delCTCA in exon 20, was detected in two unrelated patients and was associated with different clinical features. No NF1 somatic mutations were detected in the GIST tumors. A wide phenotypic and genotypic variability was registered, both in the spectrum of skin lesions and visceral neoplasms, even among members of the same family who had different clinical manifestations. A proclivity to multiple tumors arising in the same subject, and a higher tumor burden per family were the most relevant findings observed in patients affected with the NF1 mutation.</p> <p>Conclusions</p> <p>We report a novel NF1 mutation and we contribute data for the refinement of the NF1 genotype-phenotype spectrum.</p

ER Stress-Inducible Factor CHOP Affects the Expression of Hepcidin by Modulating C/EBPalpha Activity

Endoplasmic reticulum (ER) stress induces a complex network of pathways collectively termed the unfolded protein response (UPR). The clarification of these pathways has linked the UPR to the regulation of several physiological processes. However, its crosstalk with cellular iron metabolism remains unclear, which prompted us to examine whether an UPR affects the expression of relevant iron-related genes. For that purpose, the HepG2 cell line was used as model and the UPR was activated by dithiothreitol (DTT) and homocysteine (Hcys). Here, we report that hepcidin, a liver secreted hormone that shepherds iron homeostasis, exhibits a biphasic pattern of expression following UPR activation: its levels decreased in an early stage and increased with the maintenance of the stress response. Furthermore, we show that immediately after stressing the ER, the stress-inducible transcription factor CHOP depletes C/EBPα protein pool, which may in turn impact on the activation of hepcidin transcription. In the later period of the UPR, CHOP levels decreased progressively, enhancing C/EBPα-binding to the hepcidin promoter. In addition, analysis of ferroportin and ferritin H revealed that the transcript levels of these iron-genes are increased by the UPR signaling pathways. Taken together, our findings suggest that the UPR can have a broad impact on the maintenance of cellular iron homeostasis

Mechanical Properties of High and Very-High Strength Steel at Elevated Temperatures and After Cooling Down

High-strength steels (HSS) are produced using special chemical composition or/and manufacturing processes. Both aspects affect their mechanical properties at elevated temperatures and after cooling down, and particularly the residual strength and the ductility of the structural members. As HSS equates the design of lighter structural elements, higher temperatures are developed internally compared to the elements designed with conventional carbon steel. Therefore, the low thickness members, along with the severe effect of high temperature on the mechanical properties of the HSS, constitute to the increased vulnerability of such structures in fire. Moreover, the re-use and reinstatement of these structures are more challenging due to the lower residual mechanical properties of HSS after the cooling down period. This paper presents a review of the available experimental studies of the mechanical properties of HSS at elevated temperatures and after cooling down. The experimental results are collected and compared with the proposed material model (reduction factors) of EN1993–1-2. Based on these comparisons, modified equations describing the effect of elevated temperatures on the mechanical properties of HSS are proposed. Also, the post-fire mechanical properties of HSS are examined. A comprehensive discussion on the effect of influencing parameters, such as manufacturing process, microstructure, loading conditions, maximum temperature, and others is further explored

Pentraxin 3 (PTX3) Is Associated with Severe Sepsis and Fatal Disease in Emergency Room Patients with Suspected Infection: A Prospective Cohort Study

Background Early diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection. Methods The study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA). Results The median PTX3 levels in groups 1–5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (p<0.001). The median PTX3 concentration was higher in severe sepsis patients compared to others (16.7 vs. 4.9 ng/ml, p<0.001) and in non-survivors (day 28 case fatality) compared to survivors (14.1 vs. 5.1 ng/ml, p<0.001). A high PTX3 level predicted the need for ICU stay (p<0.001) and hypotension (p<0.001). AUCROC in the prediction of severe sepsis was 0.73 (95% CI 0.66–0.81, p<0.001) and 0.69 in case fatality (95% CI 0.58–0.79, p<0.001). PTX3 at a cut-off level for 14.1 ng/ml (optimal cut-off value for severe sepsis) showed 63% sensitivity and 80% specificity. At a cut-off level 7.7 ng/ml (optimal cut-off value for case fatality) showed 70% sensitivity and 63% specificity in predicting case fatality on day 28.In multivariate models, high PTX3 remained an independent predictor of severe sepsis and case fatality after adjusting for potential confounders. Conclusions A high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection.Public Library of Science open acces