Current frontiers in systemic sclerosis pathogenesis

Systemic sclerosis is an autoimmune disease characterised by vascular dysfunction, impaired angiogenesis, inflammation and fibrosis. There is no currently accepted disease‐modifying treatment with only autologous stem cell transplant showing clinically meaningful benefit. The lack of treatment options reflects our lack of understanding of the precise molecular mechanisms occurring in the disease. Recent investigations have begun to decipher the molecular pathways underpinning the different aspects of the disease and may provide a rational clinical target(s). Uncovering the molecular mechanisms of the disease is important in understanding systemic sclerosis treatment. The aim of this review was to examine the current thinking in SSc pathogenesis and will offer novel areas for research which may yield novel therapeutics.     

Transient brain ischemia due to cardiac arrest causes irreversible long-lasting cognitive injury

Lavender oil has a long history of use for treating anxiety, but only recent research has examined its effects using standard behavioural methods used to test novel drugs. The aim of this study was to investigate the effects of inhaled lavender oil on anxiety related behaviour of rats in the open field and to compare them with the effects of chlordiazepoxide (CDP), a typical anxiolytic drug. Additionally c-fos immunochemistry was used to investigate whether lavender oil produced the same pattern of c-fos expression as CDP in eight different brain areas associated with anxiety. As previously found, lavender oil showed anxiolytic properties in the open field similar to but not as extensive as those of CDP. Immunochemistry results indicated that exposure to the open field increased c-fos expression, while CDP reversed the effects of this behavioural stressor on c-fos expression in all brain regions examined except the central nucleus of the amygdala, where c-fos expression increased. Lavender oil had similar effects to CDP on the paraventricular nucleus of the hypothalamus, the dorsomedial hypothalamic nucleus and the central nucleus of the amygdala. These results strengthen the suggestion that inhaling lavender oil has anxiolytic behavioural effects, but they are weaker than the effects of benzodiazepines, and there is limited evidence that they are mediated by the same neural processes.     

Evaluation of postural balance control in patients with multiple sclerosis – effect of different sensory conditions and arithmetic task execution. A pilot study

Background and purposeThe purpose of this study was to investigate the effect of concomitant cognitive task execution and different sensory conditions on balance control in patients with multiple sclerosis (MS).Material and methodsThirty-two subjects with MS and 30 healthy age- and sex-matched control subjects were included in the study. Balance Performance Oriented Mobility Assessment was performed in all subjects. Their spontaneous sway characteristics while standing with different sensory conditions and during execution of a simple arithmetic task were analysed. Mean sway in the coronary and sagittal plane, as well as sway velocity, were measured.ResultsThe values of all evaluated variables obtained in all tests were significantly higher in the MS group than in controls. In the MS group, more pronounced progression of changes in response to increased difficulty of the test was also observed. Analysis of risk of falls in MS revealed a significant increase of sway velocity and mean sway in the mediolateral and anteroposterior plane in the majority of tests.ConclusionsPostural stability in patients with MS is significantly decreased in comparison with the control group in all evaluated conditions. Stability deficit is enhanced in response to more difficult conditions of evaluation. Increased risk of falls is related to the increased postural sway velocity and length of mean sway; this association is most pronounced in the coronary plane.     

Adjuvant vaccination with melanoma antigen-pulsed dendritic cells in stage III melanoma patients

Dendritic cells may be successfully used to induce in vivo-specific anti-tumor responses when combined with the appropriate antigen in the appropriate context. The purpose of this study was to evaluate efficacy of peptide-loaded DC vaccine in high-risk stage III melanoma patients after lymph node dissection (LND). HLA-A2⁺, -A1⁺, or -A3⁺ melanoma patients (N?=?22), stage III, N1b-N3, received 5?C16 (median: 11) DC vaccines loaded with MHC class-I-restricted melanoma peptides respective to the patient??s haplotype, and with autologous tumor lysate, if available. Vaccinated patients were matched to unvaccinated stage III controls (22 of 869) by sex, number of metastatic lymph nodes, extracapsular involvement, LND type, Breslow stage, and ulceration. Vaccination elicited cutaneous delayed-type hypersensitivity (DTH) or/and IFN-??-producing CD8⁺ cell response to melanoma peptides in 15 of 22 patients. Three-year overall survival (OS) rate was 68.2% in the vaccinated group versus 25.7% in the control group, P value accounting for matching: 0.0290. In a Cox regression model, hazard ratio (HR) for death of vaccinated patients was 0.31 [95% confidence interval (CI): 0.10?C0.94]. The corresponding values for 3-year disease-free survival rate were 40.9 versus 14.5%, P?=?0.1083; HR of recurrence for vaccinated, 0.46 (95% CI: 0.18?C1.22). There was no grade >1 toxicity. The DC/peptide vaccine was well tolerated and elicited immune responses to melanoma antigens. Vaccinated patients had significantly longer OS after LND than the matched controls, but a significant improvement in the primary endpoint DFS was not achieved.     

The conclusive role of postmortem computed tomography (CT) of the skull and computer-assisted superimposition in identification of an unknown body

Computed tomography is commonly used in modern medicine, and thus, it is often helpful for medicolegal purposes, especially as part of the antemortem record. The application of postmortem computed tomography and 3D reconstruction of the skull in challenging cases is reported, and its valuable contribution to positive identification is discussed. This paper presents a case in which the body of an unknown individual is identified. Positive identification had not been possible despite a multidisciplinary examination. The postmortem use of computerized tomography and 3D reconstruction of the skull followed by the comparison of individual morphological characteristics of the viscerocranium showed the concordant points between the deceased and a missing person. Finally, superimposition using a 3D-reconstructed skull instead of the skeletonized skull demonstrated an adequate degree of morphological consistency in the facial images of the analyzed individuals that lead to positive identification. It was concluded that where other methods of personal identification had failed, the use of postmortem computed tomography had proved to be instrumental in the positive identification of the deceased.     

The first successful fetal aortic balloon valvuloplasty in Poland

Prenatal aortic valvuloplasty is performed only in few perinatal centers in the world. Critical aortic stenosis which can lead to hypoplastic left heart syndrome or severe fetal heart failure with nonimmune hydrops is an indication for this procedure. Prenatal intervention can change the natural course of the disease. Authors present the first successful fetal balloon aortic valvuloplasty in Poland. It was performed in a 29-week fetus with critical aortic stenosis, severe impairment of left ventricular function, heart failure and fetal hydrops. After successful intervention, without any complications, left ventricular function and fetal condition improved gradually Effective fetal intervention was possible after few months of preparation and building a team of specialists. This is the first successful fetal cardiac intervention in Poland, which opens the way to the new era of fetal cardiology and hopefully will lead to improve results in children with this critical heart defect.     

Liver fat content and T2*: simultaneous measurement by using breath-hold multiecho MR imaging at 3.0 T--feasibility

Research ethics committee approval was obtained for this study, and written informed consent was obtained from all participants. The purpose was to prospectively evaluate the feasibility of breath-hold multiecho in- and out-of-phase magnetic resonance (MR) imaging for simultaneous lipid quantification and T2* measurement. A spoiled gradient-echo sequence with seven echo times alternately in phase and out of phase was used at 3.0 T. Imaging was performed in a lipid phantom, in five healthy volunteers (all men; mean age, 37 years), and in five obese individuals with hyperlipidemia or diabetes (four men, one woman; mean age, 53 years). A biexponential curve-fitting model was used to derive the relative signal contributions from fat and water, and these results were compared with results of liver proton MR spectroscopy, the reference standard. There was a significant correlation between multiecho and spectroscopic measurements of hepatic lipid concentration (r(2) = 0.99, P < .001). In vivo, the T2* of water was consistently longer than that of fat and reliably enabled the signal components to be correctly assigned. In the lipid phantom, the multiecho method could be used to determine the fat-to-water ratio and the T2* values of fat and water throughout the entire range of fat concentrations. Multiecho imaging shows promise as a method of simultaneous fat and T2* quantification.