Adverse childhood experiences, stressful life events or demographic factors: which are important in women's depression? A 2-year follow-up population study

OBJECTIVE: The aim of this study was to simultaneously test adverse background factors, namely adverse childhood experiences (ACEs), stressful life events and prior depressive symptoms, for their ability to predict recovery and non-recovery from depression in women among the general population. METHOD: A stratified random sample of women (n = 835) from the general population was collected at baseline in 1999. Depression (Beck Depression Inventory, BDI-21), ACEs and background factors were assessed by postal questionnaire at baseline. Two years later, stressful life events during the study phase, social support, use of health services and current depression (BDI > or = 13) were similarly assessed. RESULTS: Adverse childhood experiences were common among depressed women and these past experiences together with the use of health services were associated with recovery from depression. Financial difficulties and a poor subjective health status associated with non-recovery and current stressful life events increased the likelihood of depression on follow-up. Furthermore, the important variables explaining depression on follow-up were the quality of social support and the existence of prior depressive symptoms at baseline. CONCLUSIONS: Our results suggest that women's current depression especially associates with stressful life events, insufficient social support, poor subjective health and financial difficulties. It seems possible that past adverse experiences predispose women to depression, but current stressful events actualize these symptoms. In addition, use of health services are associated with recovery in women who had ACEs.     

Enhanced attention-dependent auditory processing by electroconvulsive therapy in psychotic depression

There is a lack of knowledge about the effect of electroconvulsive therapy (ECT) on auditory event-related potentials (ERPs) in severe psychotic depression. The aim of this study was to investigate both the effect of ECT on attention-dependent ERP (P300) and the correlation of P300 values with depression level. We recorded the auditory ERPs of 23 patients expressing psychotic symptoms and fulfilling the DSM-III-R criteria for treatment-resistant severe major depressive episode before and a week after successful bitemporal ECT. The clinical status was assessed with Hamilton (Ham-D) and Montgomery and Asberg (MADRS) depression scales. ECT was clinically very effective with these scales. On the level of auditory processing, ECT increased P300 amplitude with no significant effect on latency. Small amplitudes over the left hemisphere before treatment were associated with bigger Ham-D-score decrement. ECT produces a significant increase in brain activity at the level of attention-dependent auditory processing in severe depression. The change in electrical responses seems to represent a largely independent variable from the clinical assessment scales, even if the recovery rate was remarkable, because the change in overall symptom scores did not correlate with the P300 changes.     

Cross-reactivity of mimotopes with a monoclonal antibody against the high molecular weight melanoma-associated antigen (HMW-MAA) does not predict cross-reactive immunogenicity

The high molecular weight melanoma-associated antigen (HMW-MAA) is highly expressed in advanced primary and metastatic melanoma. An epitope of the core protein of HMW-MAA is recognized by the murine monoclonal antibody (mAb) 225.28S. In this study, we aimed to characterize peptides that antigenically mimicked this epitope and to determine their efficacy as components of an HMW-MAA-based anti-melanoma vaccine. Therefore, we screened a constrained 10 mer phage display peptide library against mAb 225.28S. Selected phage-displayed peptides were then tested for their specificity for the antibody's antigen-binding site. DNA sequences coding for specific peptide ligands were determined. Binding of mAb 225.28S to HMW-MAA was inhibited in a dose-dependent manner by phage-displayed peptides from 51 to 83% and by synthetic peptides from 38 to 87%. Subsequently, the immunogenicity of the five mimotopes with the highest inhibition capacity was examined in rabbits. Immunizations with synthetic mimotopes conjugated to tetanus toxoid resulted in peptide-specific antibodies, but none of the highly antigenic mimotopes induced HMW-MAA cross-reactive antibodies. This report describes an example of disparity between antigenicity and cross-reactive immunogenicity, complicating the selection of potential vaccine candidates.     

Pharmacological mechanisms contributing to the clinical efficacy of levosimendan

Acute decompensation of chronic heart failure is a direct life-threatening situation with short-term mortality approaching 30%. A number of maladaptive changes are amplified within the cardiovascular system during the progression of chronic heart failure that makes the decompensation phase difficult to handle. Levosimendan is a new Ca2+-sensitizer for the treatment of acutely decompensated heart failure that has proved to be effective during the decompensation of chronic heart failure and acute myocardial infarction. Levosimendan differs from other cardiotonic agents that are used for acute heart failure in that it utilizes a unique dual mechanism of action: Ca2+-sensitization through binding to troponin C in the myocardium, and the opening of ATP-sensitive K+ channels in vascular smooth muscle. In general, these mechanisms evoke positive inotropy and vasodilation. Clinical studies suggested long-term benefits on mortality following short-term administration. It may, therefore, be inferred that levosimendan has additional effects on the cardiovascular system that are responsible for the prolongation of survival. Results of preclinical and clinical investigations suggest that the combination of levosimendan-induced cardiac and vascular changes has favorable effects on the coronary, pulmonary and peripheral circulations. Redistribution of the circulating blood offers an improved hemodynamic context for the development of a positive inotropic effect through Ca2+-sensitization of the contractile filaments, without a proportionate increase in myocardial oxygen consumption or the development of arrhythmias. Activation of ATP-sensitive K+ channels, both on sarcolemma and mitochondria, may protect against myocardial ischemia, and decreased levels of cytokines may prevent the development of further myocardial remodeling. Collectively, these effects of levosimendan shift the disturbed cardiovascular parameters towards normalization, thereby halting the perpetuation of the vicious cycle of heart failure progression. This may contribute to stabilization of the circulation and improved life expectancy of patients with chronic heart failure.     

Influence of the washing buffer composition on the sensitivity of an enzyme-linked immunosorbent assay using mycobacterial glycolipids as capture antigens

Immunogenic glycolipids from the cell wall of Mycobacterium tuberculosis are potential capture antigens in enzyme-linked immunosorbent assays (ELISAs) for the serodiagnostis of tuberculosis. Typically, washing steps in ELISAs are performed with buffers containing a detergent. However, Tween-20, the most commonly added detergent, was reported to be able to remove the coating of certain glycolipid antigens from microtitre wells. In order to determine the influence of the washing buffer composition on the results, we measured serum immunoglobulin G (IgG) against three mycobacterial glycolipids by ELISA, conducting three separate experiments with three different buffers: Tris-buffered saline (TBS), TBS plus 0.02% Tween-20 (TBS-Tween), or TBS plus 0.3% bovine serum albumin (TBS-BSA). The capture antigens applied were lipoarabinomannan with the basic arabinose-containing motif (AraLAM), the mannose-capped version of lipoarabinomannan (ManLAM), and trehalose-6,6'-dimycolate (cord factor). All ELISAs achieved acceptable specificities around 95%. The sensitivities, however, varied widely, depending upon the sort of washing buffer used. In 38 patients with sputum smear-positive pulmonary tuberculosis and control groups of 79 patients with non-tuberculosis lung disease and 92 healthy volunteers, the anti-cord factor ELISA achieved 100%, 31.6%, and 60.5% with TBS, TBS-Tween, and TBS-BSA, respectively. Corresponding sensitivity values for AraLAM were 39.5%, 26.3%, and 23.7%, and for ManLAM 94.7%, 65.8%, and 55.3%. We conclude that Tween-20 or BSA should be omitted from the washing buffer in ELISAs, when the capture antigen is of lipid nature.     

Somatoform dissociation and adverse childhood experiences in the general population

Childhood trauma has been associated with psychological dissociation, but there is evidence that trauma may also result in somatoform dissociation. We performed a general population study with 1739 subjects, using the Somatoform Dissociation Questionnaire, measures of adverse childhood experiences, and sociodemographic background. The prevalence of high somatoform dissociation (Somatoform Dissociation Questionnaire >or=30) was 9.4% in the Finnish general population. Unemployment, a reduced working ability, and a poor financial situation were associated with high somatoform dissociation. Of the adverse childhood experiences, high somatoform dissociation was strongly linked to physical punishment but not associated with domestic violence, including sexual and physical abuse. The odds of high somatoform dissociation were also increased among men by a poor relationship between their parents, and among women by alcohol abuse in their childhood home. We found a strong, graded relationship between an increasing number of adverse childhood experiences and high somatoform dissociation.     

Expression of the B subunit of the heat-labile enterotoxin of Escherichia coli in tobacco mosaic virus-infected Nicotiana benthamiana plants and its characterization as mucosal immunogen and adjuvant

We have produced biologically active recombinant (r) LTB, the nontoxic B subunit of heat-labile toxin (LT) of Escherichia coli in tobacco mosaic virus (TMV)-infected Nicotiana benthamiana plants. We amplified the LTB encoding sequence with its leader and introduced a hexahistidyl tag and an endoplasmic reticulum retention signal. The resulting product was ligated into a TMV-based plant viral expression vector that was used for the generation of recombinant viral RNA. Eighty-nine percent of N. benthamiana plants inoculated with the recombinant viral RNA were systemically infected as determined by anti-TMV enzyme-linked immunosorbent assay (ELISA) experiments. The rLTB monomer was identified by LT-specific as well as by histidyl-tag-specific immunoblots. rLTB from plant extracts of TMV-infected N. benthamiana leaves was purified to give 75 microg rLTB pentamers per gram fresh plant material and was capable of binding G(M)1 ganglioside. The immunogenicity of the plant-produced rLTB was tested in mice and showed that intranasal application of rLTB (15 microg per mouse) induced LTB-specific IgG1 antibodies. To prove its adjuvanticity, rLTB was intranasally co-administered with the Hevea latex allergen Hev b 3, leading to allergen-specific IgG1 and IgG2a antibody production. The fact that intranasal application of rLTB and Hev b 3 prior to systemic challenge with the allergen enhanced the Th2 responses at the humoral and cellular level indicated that rLTB promoted immune responses that were naturally induced by the antigen/allergen. In conclusion, these results indicate that the plant viral expression system is suitable for the rapid large-scale production of biologically active LTB with strong mucosal adjuvant capacity.     

Antimicrobial susceptibility and macrolide resistance genes in Streptococcus pyogenes collected in Austria and Hungary

A total of 341 clinical isolates of Streptococcus pyogenes from Vienna, Austria and three Hungarian cities were tested for susceptibility to four macrolides and 12 other antibiotics. All isolates were fully susceptible to penicillin and the other beta-lactams tested. A high level of tetracycline resistance was found in Austria (26.7%) and in Hungary (30.5%). The rate of resistance to erythromycin, clarithromycin and azithromycin was 4.7% in Vienna and 3.7% in the Hungarian communities. In both countries, the MIC(90) values of erythromycin and clarithromycin were 0.12 mg/L and the MIC(90) of josamycin was 0.5mg/L. The M phenotype of resistance conferred by the mefA genes was predominant (n = 9) among the macrolide-resistant isolates (n = 14).     

Application of recombinant activated factor VII during surgery for a giant skull base hemangiopericytoma to achieve safe hemostasis. Case report

The authors report on a 64-year-old woman with a huge recurrent skull base hemangiopericytoma, in whom they encountered severe difficulty in attaining intraoperative hemostasis. Standard surgical hemostatic methods and the administration of fresh-frozen plasma and prothrombin complex concentrates failed to stop diffuse bleeding from an inoperable tumor remnant. At a critical point during the operation, the intravenous administration of recombinant activated factor VII, combined with mechanical compression, finally led to satisfactory hemostasis. The rationale for using recombinant activated factor VII in situations of uncontrolled bleeding during neurosurgical procedures is discussed, along with the literature in which the use of recombinant activated factor VII as a maneuver of last resort is reported for hemostasis in other surgical fields.