Continuing bonds and place

Where do people feel closest to those they have lost? This article explores how continuing bonds with a deceased person can be rooted in a particular place or places. Some conceptual resources are sketched, namely continuing bonds, place attachment, ancestral places, home, reminder theory, and loss of place. The authors use these concepts to analyze interview material with seven Swedes and five Britons who often thought warmly of the deceased as residing in a particular place and often performing characteristic actions. The destruction of such a place, by contrast, could create a troubling, haunting absence, complicating the deceased’s absent-presence.     

A large-scale genome-wide gene expression analysis in peripheral blood identifies very few differentially expressed genes related to antidepressant treatment and response in patients with major depressive disorder

A better understanding of the biological factors underlying antidepressant treatment in patients with major depressive disorder (MDD) is needed. We perform gene expression analyses and explore sources of variability in peripheral blood related to antidepressant treatment and treatment response in patients suffering from recurrent MDD at baseline and after 8 weeks of treatment. The study includes 281 patients, which were randomized to 8 weeks of treatment with vortioxetine (N = 184) or placebo (N = 97). To our knowledge, this is the largest dataset including both gene expression in blood and placebo-controlled treatment response measured by a clinical scale in a randomized clinical trial. We identified three novel genes whose RNA expression levels at baseline and week 8 are significantly (FDR < 0.05) associated with treatment response after 8 weeks of treatment. Among these genes were SOCS3 (FDR = 0.0039) and PROK2 (FDR = 0.0028), which have previously both been linked to depression. Downregulation of these genes was associated with poorer treatment response. We did not identify any genes that were differentially expressed between placebo and vortioxetine groups at week 8 or between baseline and week 8 of treatment. Nor did we replicate any genes identified in previous peripheral blood gene expression studies examining treatment response. Analysis of genome-wide expression variability showed that type of treatment and treatment response explains very little of the variance, a median of <0.0001% and 0.05% in gene expression across all genes, respectively. Given the relatively large size of the study, the limited findings suggest that peripheral blood gene expression might not be the best approach to explore the biological factors underlying antidepressant treatment.Subject terms: Predictive markers, Depression     

Sliding free transverse rectus abdominis myocutaneous flap for closure of a massive abdominal wall defect: A case report

Despite considerable advances in reconstructive surgery, massive abdominal wall defects continue to pose a significant surgical challenge. We report the case of a 72‐year‐old morbidly obese female patient with Clostridium septicum‐related gas gangrene of the abdominal wall. After multidisciplinary treatment and multiple extensive debridements, a massive full‐thickness defect (40 cm × 35 cm) of the right abdominal wall was present. The abdominal contents were covered with a resorbable mesh to prevent evisceration. Finally, the composite defect was successfully reconstructed through a contralateral extended free transverse rectus abdominis myocutaneus (TRAM) flap (50 cm × 38 cm). An arterio‐venous loop to the superficial femoral vessels using the great saphenous vein was necessary to allow the flap to reach the defect. Postoperatively, a minor wound healing disorder of the flap was successfully treated with split skin grafting. Six month after surgery, the patient presented with a completely healed flap coverage area and a small abdominal hernia without the need of further surgical revision. This case illustrates the use of a sliding free TRAM flap for closure of a massive abdominal wall defect.     

Lymphocyte Subpopulations,Oxidative Burst and Apoptosis in Peripheral Blood Cells of Patients with Multiple Sclerosis–Effect of Interferon-β

At present, the most efficient therapeutical treatment of multiple sclerosis (MS) is achieved by IFN-β. However, its in vivo effects remain incompletely understood. If applied parenterally, the hydrophobic IFN-β acts primarily on blood cells with probable selectivity for functionally different lymphocyte subpopulations, monocytes and granulocytes. We have investigated the expression of the activation marker interleukin-2 receptor-α (CD25) on CD3⁺ T cells, CD19⁺ B cells, foetal-type γδ⁺CD3⁺ T cells and foetal-type CD5⁺CD19⁺ B cells of the peripheral blood. In addition, the oxidative burst activity and apoptosis have been determined in mononuclear and polymorphonuclear blood cells, respectively. The study accompanied a phase III trial with IFN-β1b (BETAFERON^®, Schering). Two groups of MS patients with relapsing-remitting course of the disease have been investigated at 8 time points (days 0, 5, 15, 31, 60, 90, 180 and 270 after starting therapy): (1) verum group (n=8) with application of 8 Mill. units IFN-β1b every other day, and (2) placebo group (n=4) with application of placebo for 3 months and therapy as in (1) from day 90 onward. The main results were: (1) Activated T cells decreased until day 180 in the verum group and return thereafter to pre-treatment values, whereas in the placebo group the values remained relatively stable over the whole observation period. (2) Activated B cells increased between days 90 and 270 in both groups, i.e. after verum application in both groups. (3) Foetal-type B cells were more activated than total B and T cells with increase over time in both groups. (4) Foetal-type T cells exerted relatively stable intra-individual levels with generally low CD25 expression, but punctual CD25 peaks in both groups. (5) The spontaneous oxidative burst was higher in lymphocytes, more variable in monocytes and faster increasing in granulocytes in the verum group than in the placebo group. (6) Apoptosis of mononuclear cells and granulocytes showed similar variations in the verum and placebo groups with the exception of a selective increase over time of the proportion of granulocytes undergoing induced apoptosis in the verum group. It is concluded that IFN-β has the following main effects on the immune system of MS patients: (1) the T cell immunity is systemically and reversibly suppressed, (2) the foetal-type lymphocytes, which are responsible for the first line of defence of infections, are stimulated in the long range, (3) the oxidative burst activity is increased in lymphocytes and granulocytes and instable in monocytes, and (4) the inducibility of apoptosis in granulocytes is increased. Re-examination of the altered blood cell parameters after long-term IFN-β therapy is warranted.     

Molecular imaging reveals time course of matrix metalloproteinase activity in acute cutaneous vasculitis in vivo

Matrix metalloproteinases (MMPs) play a critical role in various pathological conditions including cutaneous inflammation. Thus far, serial assessment of MMP activity in ongoing inflammation is hampered due to technical limitations. Here, we present an innovative method for longitudinal detection of MMP activity by in vivo imaging. First, we analysed skin sections from patients suffering from leucocytoclastic vasculitis (LcV) and detected a significant MMP signal via immunofluorescence staining. Then, we mimicked LcV in mice in a well‐studied model of immune complex‐mediated vasculitis (ICV). This acute inflammatory process was serially visualized in vivo using the fluorescence‐labelled MMP tracer Cy5.5‐AF443. The deposition of fluorescence‐labelled immune complexes and MMP tracer distribution was visualized repeatedly and non‐invasively by fluorescence reflectance imaging. In correlation with the presence of MMP‐2 and MMP‐9 in immunofluorescence stainings, Cy5.5‐AF443 accumulated in ICV spots in the skin of C57BL/6 mice. This tracer accumulation could also be observed in mice equipped with a dorsal skinfold chamber, where microscopic observations revealed an increased recruitment of fluorescence‐labelled leucocytes during ICV. The specificity of the MMP tracer was supported by (i) analysis of mice deficient in functional β₂‐integrins (CD18^?/?) and (ii) subsequent MMP immunofluorescence staining. These findings let us conclude that MMP accumulation in the acute phase of ICV depends on β₂‐mediated leucocyte recruitment. In summary, we show that MMPs are involved in ICV as determined by Cy5.5‐AF443, a new optical marker to longitudinally and non‐invasively follow MMP activity in acute skin inflammation in vivo.