Initial evaluation and follow-up of acute radiation syndrome in two patients from the Dakar accident

The aim of this work was to evaluate and follow up the evolution of radiation damage in two victims of a radiation accident. Blood samples were used for cytogenetic evaluation of radiation dose and heterogeneity. The radiation dose estimates were 1 Gy and 2.3 Gy in the two most exposed patients. Plasma was used for the measurement of the Flt3 ligand as a marker of haematopoietic aplasia, citrulline for damage to the jejunal mucosal epithelium and oxysterols for damage to the liver, the central nervous system and the vascular compartment. The use of these biological indicators demonstrated the presence of a haematopoietic syndrome and suggested the presence of subclinical radiation-induced damage to the liver in one of the two patients. These results support the interest in using these biological indicators in order to evaluate radiation damage, especially in complex accidental situations.     

IgM production by bone marrow plasmablasts contributes to long-term protection against intracellular bacterial infection

IgM responses are well known to occur early postinfection and tend to be short-lived, which has suggested that this Ig does not significantly contribute to long-term immunity. In this study, we demonstrate that chronic infection with the intracellular bacterium Ehrlichia muris elicits a protective, long-term IgM response. Moreover, we identified a population of CD138(high)IgM(high) B cells responsible for Ag-specific IgM production in the bone marrow. The IgM-secreting cells, which exhibited characteristics of both plasmablasts and plasma cells, contributed to protection against fatal ehrlichial challenge. Mice deficient in activation-induced cytidine deaminase, which produce only IgM, were protected against fatal ehrlichial challenge infection. The IgM-secreting cells that we have identified were maintained in the bone marrow in the absence of chronic infection, as antibiotic-treated mice remained protected against challenge infection. Our studies identify a cell population that is responsible for the IgM production in the bone marrow, and they highlight a novel role for IgM in the maintenance of long-term immunity during intracellular bacterial infection.     

Prevalence of and risk factors for persistent postoperative nonanginal pain after cardiac surgery: a 2-year prospective multicentre study

Background:

Persistent postoperative pain continues to be an underrecognized complication. We examined the prevalence of and risk factors for this type of pain after cardiac surgery.

Methods:

We enrolled patients scheduled for coronary artery bypass grafting or valve replacement, or both, from Feb. 8, 2005, to Sept. 1, 2009. Validated measures were used to assess (a) preoperative anxiety and depression, tendency to catastrophize in the face of pain, health-related quality of life and presence of persistent pain; (b) pain intensity and interference in the first postoperative week; and (c) presence and intensity of persistent postoperative pain at 3, 6, 12 and 24 months after surgery. The primary outcome was the presence of persistent postoperative pain during 24 months of follow-up.

Results:

A total of 1247 patients completed the preoperative assessment. Follow-up retention rates at 3 and 24 months were 84% and 78%, respectively. The prevalence of persistent postoperative pain decreased significantly over time, from 40.1% at 3 months to 22.1% at 6 months, 16.5% at 12 months and 9.5% at 24 months; the pain was rated as moderate to severe in 3.6% at 24 months. Acute postoperative pain predicted both the presence and severity of persistent postoperative pain. The more intense the pain during the first week after surgery and the more it interfered with functioning, the more likely the patients were to report persistent postoperative pain. Pre-existing persistent pain and increased preoperative anxiety also predicted the presence of persistent postoperative pain.

Interpretation:

Persistent postoperative pain of nonanginal origin after cardiac surgery affected a substantial proportion of the study population. Future research is needed to determine whether interventions to modify certain risk factors, such as preoperative anxiety and the severity of pain before and immediately after surgery, may help to minimize or prevent persistent postoperative pain.Postoperative pain that persists beyond the normal time for tissue healing (> 3 mo) is increasingly recognized as an important complication after various types of surgery and can have serious consequences on patients’ daily living.^1–3 Cardiac surgeries, such as coronary artery bypass grafting (CABG) and valve replacement, rank among the most frequently performed interventions worldwide.⁴ They aim to improve survival and quality of life by reducing symptoms, including anginal pain. However, persistent postoperative pain of nonanginal origin has been reported in 7% to 60% of patients following these surgeries.^5–23 Such variability is common in other types of major surgery and is due mainly to differences in the definition of persistent postoperative pain, study design, data collection methods and duration of follow-up.^1–3,24Few prospective cohort studies have examined the exact time course of persistent postoperative pain after cardiac surgery, and follow-up has always been limited to a year or less.^9,14,25 Factors that put patients at risk of this type of problem are poorly understood.²⁶ Studies have reported inconsistent results regarding the contribution of age, sex, body mass index, preoperative angina, surgical technique, grafting site, postoperative complications or level of opioid consumption after surgery.^{5–7,9,13,14,16–19,21–23,25,27} Only 1 study investigated the role of chronic nonanginal pain before surgery as a contributing factor;²¹ 5 others prospectively assessed the association between persistent postoperative pain and acute pain intensity in the first postoperative week but reported conflicting results.^{13,14,21,22,25} All of the above studies were carried out in a single hospital and included relatively small samples. None of the studies examined the contribution of psychological factors such as levels of anxiety and depression before cardiac surgery, although these factors have been shown to influence acute or persistent postoperative pain in other types of surgery.^1,24,28,29We conducted a prospective multicentre cohort study (the CARD-PAIN study) to determine the prevalence of persistent postoperative pain of nonanginal origin up to 24 months after cardiac surgery and to identify risk factors for the presence and severity of the condition.     

Finite element investigation of the loading rate effect on the spinal load-sharing changes under impact conditions

Sudden deceleration and frontal/rear impact configurations involve rapid movements that can cause spinal injuries. This study aimed to investigate the rotation rate effect on the L2–L3 motion segment load-sharing and to identify which spinal structure is at risk of failure and at what rotation velocity the failure may initiate?Five degrees of sagittal rotations at different rates were applied in a detailed finite-element model to analyze the responses of the soft tissues and the bony structures until possible fractures. The structural response was markedly different under the highest velocity that caused high peaks of stresses in the segment compared to the intermediate and low velocities. Under flexion, the stress was concentrated at the upper pedicle region of L2 and fractures were firstly initiated in this region and then in the lower endplate of L2. Under extension, maximum stress was located in the lower pedicle region of L2 and fractures started in the left facet joint, then they expanded in the lower endplate and in the pedicle region of L2. No rupture has resulted at the lower or intermediate velocities. The intradiscal pressure was higher under flexion and decreased when the endplate was fractured, while the contact forces were greater under extension and decreased when the facet surface was cracked. The highest ligaments stresses were obtained under flexion and did not reach the rupture values. The endplate, pedicle and facet surface represented the potential sites of bone fracture. Results showed that spinal injuries can result at sagittal rotation velocity exceeding 0.5°/ms.     

Role of HIV-1 RNA and protein determinants for the selective packaging of spliced and unspliced viral RNA and host U6 and 7SL RNA in virus particles

HIV-1 particles contain RNA species other than the unspliced viral RNA genome. For instance, viral spliced RNAs and host 7SL and U6 RNAs are natural components that are non-randomly incorporated. To understand the mechanism of packaging selectivity, we analyzed the content of a large panel of HIV-1 variants mutated either in the 5'UTR structures of the viral RNA or in the Gag-nucleocapsid protein (GagNC). In parallel, we determined whether the selection of host 7SL and U6 RNAs is dependent or not on viral RNA and/or GagNC. Our results reveal that the polyA hairpin in the 5'UTR is a major packaging determinant for both spliced and unspliced viral RNAs. In contrast, 5'UTR RNA structures have little influence on the U6 and 7SL RNAs, indicating that packaging of these host RNAs is independent of viral RNA packaging. Experiments with GagNC mutants indicated that the two zinc-fingers and N-terminal basic residues restrict the incorporation of the spliced RNAs, while favoring unspliced RNA packaging. GagNC through the zinc-finger motifs also restricts the packaging of 7SL and U6 RNAs. Thus, GagNC is a major contributor to the packaging selectivity. Altogether our results provide new molecular insight on how HIV selects distinct RNA species for incorporation into particles.     

Characterization of the elongasome core PBP2 : MreC complex of Helicobacter pylori

The definition of bacterial cell shape is a complex process requiring the participation of multiple components of an intricate macromolecular machinery. We aimed at characterizing the determinants involved in cell shape of the helical bacterium Helicobacter pylori. Using a yeast two-hybrid screen with the key cell elongation protein PBP2 as bait, we identified an interaction between PBP2 and MreC. The minimal region of MreC required for this interaction ranges from amino acids 116 to 226. Using recombinant proteins, we showed by affinity and size exclusion chromatographies and surface plasmon resonance that PBP2 and MreC form a stable complex. In vivo, the two proteins display a similar spatial localization and their complex has an apparent 1:1 stoichiometry; these results were confirmed in vitro by analytical ultracentrifugation and chemical cross-linking. Small angle X-ray scattering analyses of the PBP2 : MreC complex suggest that MreC interacts directly with the C-terminal region of PBP2. Depletion of either PBP2 or MreC leads to transition into spherical cells that lose viability. Finally, the specific expression in trans of the minimal interacting domain of MreC with PBP2 in the periplasmic space leads to cell rounding, suggesting that the PBP2/MreC complex formation in vivo is essential for cell morphology.