Effect of gender on suicide attempters versus nonattempters in an adolescent inpatient unit

BACKGROUND: Although gender differences have been noted in the risk factors for suicide and attempted suicide, comparative studies to date have used only 2 groups and a limited number of measures. The present study compared the effect of gender on suicide among 4 groups of psychiatrically hospitalized adolescents using a cross-sectional design. METHODS: The study sample consisted of 404 patients, aged between 12 and 21, who were divided into 4 groups: 76 male suicide attempters, 103 male nonattempters, 143 female suicide attempters, and 82 female nonattempters. Patients were tested for life events, affective disorders, aggression, impulsivity, ego defense mechanisms, and death perception with the Child Suicide Potential Scale, Beck Depression Inventory, State-Trait Anxiety Inventory, Overt Aggression Scale, Multidimensional Anger Inventory, Impulsivity Control Scale, and Life Style Index. Findings were analyzed by multivariate regression with stepwise logistic models. RESULTS: Depression and anxiety were more prevalent in female nonattempters than in male nonattempters; there were no such gender differences among the attempters. Antisocial behavior was more prevalent in male attempters than in female attempters; there were no gender differences on this aspect among the nonattempters. There were gender differences for defense mechanisms in the attempters. Logistic regression models for men and women separately revealed that antisocial behavior and anxiety were common predictors of suicide attempt, that destructiveness was a predictor in women only, and that depression was associated with suicide attempt in men only. CONCLUSIONS: Suicide-prone female and male adolescent inpatients show distinct differences in psychopathology, ego defense mechanisms, and life events compared to psychiatrically hospitalized adolescents without any history of suicide attempt. Any deviation from a gender-specific behavior must raise suspicion of a risk of attempted suicide.     

Reverse Engineering of the Spindle Assembly Checkpoint

The Spindle Assembly Checkpoint (SAC) is an intracellular mechanism that ensures proper chromosome segregation. By inhibiting Cdc20, a co-factor of the Anaphase Promoting Complex (APC), the checkpoint arrests the cell cycle until all chromosomes are properly attached to the mitotic spindle. Inhibition of Cdc20 is mediated by a conserved network of interacting proteins. The individual functions of these proteins are well characterized, but understanding of their integrated function is still rudimentary. We here describe our attempts to reverse-engineer the SAC network based on gene deletion phenotypes. We begun by formulating a general model of the SAC which enables us to predict the rate of chromosomal missegregation for any putative set of interactions between the SAC proteins. Next the missegregation rates of seven yeast strains are measured in response to the deletion of one or two checkpoint proteins. Finally, we searched for the set of interactions that correctly predicted the observed missegregation rates of all deletion mutants. Remarkably, although based on only seven phenotypes, the consistent network we obtained successfully reproduces many of the known properties of the SAC. Further insights provided by our analysis are discussed.     

Role of ASCA and the NOD2/CARD15 mutation Gly908Arg in predicting increased surgical costs in Crohn's disease patients: a project of the European Collaborative Study Group on Inflammatory Bowel Disease

BACKGROUND: NOD2/CARD15, the first identified susceptibility gene in Crohn's disease (CD), is associated with ileal stenosis and increased frequency of surgery. Anti-Saccharomyces cerevisiae antibody (ASCA), a serological marker for CD, is associated with ileal location and a high likelihood for surgery. We hypothesized that the presence of ASCA and NOD2/CARD15 mutations could predict increased health care cost in CD. METHODS: CD patients in a prospectively designed community-based multinational European and Israeli cohort (n = 228) followed for mean 8.3 (SD 2.6) years had blood drawn for measurement of ASCA (IgG, IgA), Arg702Trp, Gly908Arg, and Leu1007fsinsC. Days spent in the hospital and the costs of medical and surgical hospitalizations and medications were calculated. RESULTS: The median duration of surgical hospitalizations was longer in Gly908Arg-positive than -negative patients, 3.5 and 1.5 days/patient-year (P < 0.01), and in ASCA-positive than -negative patients, 1.1 and 0 days/patient-year (P < 0.001). Median surgical hospitalization cost was 1,580 euro/patient-year in Gly908Arg-positive versus 0 euro/patient-year in -negative patients (P < 0.01), and 663 euro/patient-year in ASCA-positive versus 0 euro/patient-year in -negative patients (P < 0.001). Differences in cost of medications between groups were not significant. The effect of Gly908Arg was expressed in countries with higher Gly908Arg carriage rates. ASCA raised surgical costs independently of the age at diagnosis of disease. Arg702Trp and Leu1007fsinsC did not affect the cost of health care. CONCLUSIONS: Since CD patients positive for Gly908Arg and ASCA demonstrated higher health care costs, it is possible that measurement of Gly908Arg and ASCA at disease diagnosis can forecast the expensive CD patients.     

The Aetiology of Subacromial Impingement Syndrome

Subacromial impingement syndrome is one of the most common causes of shoulder pathology (Jobe and Jobe, 1983; Kessel and Watson, 1977) with reference to the condition appearing in the literature approximately 150 years ago (Adams, 1852). The pain and dysfunction associated with SIS are generally considered to occur when the shoulder is placed in positions of elevation, an activity commonplace during many sporting and vocational pursuits, as well as during the activities involved in daily living.Although it has been popular to assign blame for this condition on the acromion, considerable evidence suggests that SIS is of multifactorial aetiology. Other factors include rotator cuff over-use and degen-eration, glenohumeral hypermobility and instability, restrictive processes of the shoulder, functional scapular instability as well as poor posture. Many of these models of impingement still remain hypothetical and require confirmation.Further, many other structures may refer symptoms to the shoulder and may mimic the symptoms of SIS. Each category of subacromial impingement may require its own specific treatment and rehabilitation programme. At present there is not enough evidence in the literature to determine the most appropriate assessment methods or treatment strategies for each category of impingement. Key Messages

▪ Subacromial impingement syndrome has been described as the most common form of shoulder pathology.

▪ The pain of subacromial impingement is generally experienced around the anterolateral aspect of the shoulder during activities involving shoulder elevation.

▪ The aetiology of subacromial impingement syndrome is multifactorial. Each potential cause may act independently or in combination with one another.

The effect of angulation in abdominal aortic aneurysms: fluid–structure interaction simulations of idealized geometries

Abdominal aortic aneurysm (AAA) represents a degenerative disease process of the abdominal aorta that results in dilation and permanent remodeling of the arterial wall. A fluid structure interaction (FSI) parametric study was conducted to evaluate the progression of aneurysmal disease and its possible implications on risk of rupture. Two parametric studies were conducted using (i) the iliac bifurcation angle and (ii) the AAA neck angulation. Idealized streamlined AAA geometries were employed. The simulations were carried out using both isotropic and anisotropic wall material models. The parameters were based on CT scans measurements obtained from a population of patients. The results indicate that the peak wall stresses increased with increasing iliac and neck inlet angles. Wall shear stress (WSS) and fluid pressure were analyzed and correlated with the wall stresses for both sets of studies. An adaptation response of a temporary reduction of the peak wall stresses seem to correlate to a certain extent with increasing iliac angles. For the neck angulation studies it appears that a breakdown from symmetric vortices at the AAA inlet into a single larger vortex significantly increases the wall stress. Our parametric FSI study demonstrates the adaptation response during aneurysmal disease progression and its possible effects on the AAA risk of rupture. This dependence on geometric parameters of the AAA can be used as an additional diagnostic tool to help clinicians reach informed decisions in establishing whether a risky surgical intervention is warranted.     

Immune phenomena involved in the in vivo regression of fibrosarcoma cells expressing cell-associated IL-1alpha

Constitutive expression of cell-associated, but not secreted, interleukin-1alpha (IL-1alpha) by oncogene-transformed fibrosarcoma cells induced regressing tumors in mice, a phenomenon that was abrogated by the IL-1 inhibitor, the IL-1 receptor antagonist (IL-1Ra). On the contrary, non-IL-1alpha-expressing tumor cells induce progressive tumors in mice. In vivo and ex vivo experiments have shown that regression of IL-1alpha-positive fibrosarcoma cells depends on CD8(+) T cells, which can also be activated in CD4(+) T cell-depleted mice, with some contribution of natural killer cells. In spleens of mice bearing the non-IL-1alpha-expressing fibrosarcoma cells, some early and transient manifestations of antitumor-specific immunity, such as activation of specific proliferating T cells, are evident; however, no development of cytolytic T lymphocytes or other antitumor protective cells could be detected. In spleens of mice bearing the non-IL-1alpha-expressing fibrosarcoma cells, the development of early tumor-mediated suppression was observed, and in spleens of mice injected with IL-1alpha-positive fibrosarcoma cells, protective immunity developed in parallel to tumor regression. Treatment of mice bearing violent fibrosarcoma tumors with syngeneic-inactivated, IL-1alpha-positive fibrosarcoma cells, at a critical interval after injection of the malignant cells (Days 5-12), induced tumor regression, possibly by potentiating and amplifying transient antitumor cell immune responses or by ablation of tumor-mediated suppression. Membrane-associated IL-1alpha may thus serve as an adhesion molecule, which allows efficient cell-to-cell interactions between the malignant and immune effector cells that bear IL-1Rs and function as a focused cytokine with adjuvant activities at nontoxic, low levels of expression. Our results also point to the potential of using antitumor immunotherapeutic approaches using cell-associated IL-1alpha.     

Astrocytes facilitate melanoma brain metastasis via secretion of IL‐23

Melanoma is the leading cause of skin cancer mortality. The major cause of melanoma mortality is metastasis to distant organs, frequently to the brain. The microenvironment plays a critical role in tumourigenesis and metastasis. In order to treat or prevent metastasis, the interactions of disseminated tumour cells with the microenvironment at the metastatic organ have to be elucidated. However, the role of brain stromal cells in facilitating metastatic growth is poorly understood. Astrocytes are glial cells that function in repair and scarring of the brain following injury, in part via mediating neuroinflammation, but the role of astrocytes in melanoma brain metastasis is largely unresolved. Here we show that astrocytes can be reprogrammed by human brain‐metastasizing melanoma cells to express pro‐inflammatory factors, including the cytokine IL‐23, which was highly expressed by metastases‐associated astrocytes in vivo. Moreover, we show that the interactions between astrocytes and melanoma cells are reciprocal: paracrine signalling from astrocytes up‐regulates the secretion of the matrix metalloproteinase MMP2 and enhances the invasiveness of brain‐metastasizing melanoma cells. IL‐23 was sufficient to increase melanoma cell invasion, and neutralizing antibodies to IL‐23 could block this enhanced migration, implying a functional role for astrocyte‐derived IL‐23 in facilitating the progression of melanoma brain metastasis. Knocking down the expression of MMP2 in melanoma cells resulted in inhibition of IL‐23‐induced invasiveness. Thus, our study demonstrates that bidirectional signalling between melanoma cells and astrocytes results in the formation of a pro‐inflammatory milieu in the brain, and in functional enhancement of the metastatic potential of disseminated melanoma cells. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Increased thromboembolic incidence in anti-cardiolipin-positive patients with malignancy.

This study was undertaken to determine the prevalence of anti-cardiolipin antibodies (ACLAs) in patients with malignancy and to investigate a possible association of ACLAs with thromboembolic events in such patients. The study included 216 patients with solid and non-solid malignancies and an age-matched control group of 88 healthy subjects. ACLA levels were measured and related to thromboembolic phenomena (diagnosed by imaging methods) that occurred within 12 months of the diagnosis of cancer. Forty-seven patients (approximately 22%) with cancer were ACLA positive as compared with only three subjects (approximately 3%) in the control group (P < 0.0001). The ACLA-positive cancer patients had a significantly higher rate of thromboembolic events than ACLA-negative cancer patients: 13 of 47 (28%) vs 24 of 169 (14%), respectively (P < 0.05). High titres of either IgG-ACLA or IgM-ACLA were found in 10 out of 13 ACLA-positive cancer patients with thrombotic complications, but in only 2 out of 34 cancer ACLA-positive patients without thromboembolic events (P < 0.0001). In four cancer patients in whom ACLA levels were followed ACLA decreased after successful surgery/chemotherapy treatment and remained negative and thromboembolic free for 12 months of follow-up. Patients with malignancies show an increased prevalence of ACLA. Furthermore, ACLA-positive patients, mainly those with high titres, are much more prone to thromboembolic events.