Macrophage migration inhibitory factor in systemic lupus erythematosus

OBJECTIVE: To examine associations between serum macrophage migration inhibitory factor (MIF) and disease-related variables and corticosteroid use in patients with systemic lupus erythematosus (SLE). METHODS: Serum MIF concentration was measured by ELISA in 90 female patients with SLE and 279 healthy controls. Univariate and multivariate regression analyses were used to examine the associations between serum MIF concentration and disease-related indices of SLE and corticosteroid use. RESULTS: Serum MIF concentrations were positively associated with SLE disease damage (SLICC/ACR index), and indices of disease damage were greater in SLE patients with serum MIF concentrations above the normal median value. Serum MIF concentration was also observed to be significantly greater in patients with SLICC/ACR damage index (DI) scores >/= 3. Serum MIF was also positively associated with current corticosteroid dose. Significantly higher SLICC/ACR DI scores were observed in patients with values of serum MIF above the normal median, and this remained significant after adjusting for corticosteroid dose. Serum MIF concentration was also predictive of SLICC/ACR index after 3 years of followup, but this association was partly confounded by corticosteroid dose. Serum MIF was also negatively associated with serum creatinine concentration, independent of disease damage and corticosteroid dose. CONCLUSION: MIF is overexpressed in patients with SLE. While this can be partly explained by corticosteroid use, there is evidence of an association between MIF and lupus-related disease damage.     

Human angiogenic cell precursors restore function in the infarcted rat heart: a comparison of cell delivery routes

BACKGROUND: We recently isolated angiogenic cell precursors (ACPs) from human blood, which can induce angiogenesis in vitro. AIMS: In the present study, we used a nude rat model of ischaemic cardiomyopathy to compare the efficacy of intramyocardial and intracoronary ACP implantation, and to evaluate effects on cardiac function, scar size and angiogenesis. METHODS AND RESULTS: Adult nude rats underwent coronary artery ligation. Six days later, ACPs (characterized in vitro prior to implantation) or culture media were injected directly into the ischaemic myocardial region or into the coronary artery via the aorta. Cardiac function was measured by echocardiography prior to and at 2 and 4 weeks after implantation. Scar morphology, cell engraftment, and myocardial angiogenesis were evaluated at 4 weeks. Two and four weeks after implantation, cardiac function declined in both of the control groups but improved in both the intramyocardial and intracoronary ACP groups. Significant reductions in myocardial scar area were only observed in the intramyocardial ACP group, while increases in blood vessel density, which were observed in all ACP recipients, were greatest in the intracoronary ACP group. CONCLUSIONS: Human ACPs, delivered via intramyocardial or intracoronary injection, engrafted into damaged cardiac tissue and improved cardiac function within 4 weeks through effects on scar morphology and blood vessel formation.     

Platelet formation is the consequence of caspase activation within megakaryocytes

Platelets are formed from mature megakaryocytes (MKs) and arise from the development of long and thin cytoplasmic extensions called proplatelets. After platelet release, the senescent MKs (nucleus surrounded by some cytoplasm) undergo cell death by apoptosis. To explore the precise role of apoptosis in proplatelet formation, we grew human MKs from CD34(+) cells and assessed the possible role of caspases. Proteolytic maturation of procaspase-3 and procaspase-9 was detected by immunoblots in maturing MKs as well as in proplatelet-bearing MKs and senescent MKs. Cleavage of caspase substrates such as gelsolin or poly adenosine diphosphate (ADP)-ribose polymerase (PARP) was also detected. Interestingly, activated forms of caspase-3 were detected in maturing MKs, before proplatelet formation, with a punctuate cytoplasmic distribution, whereas a diffuse staining pattern was seen in senescent and apoptotic MKs. This localized activation of caspase-3 was associated with a mitochondrial membrane permeabilization as assessed by the release of cytochrome c, suggesting an activation of the intrinsic pathway. Moreover, these MKs with localized activated caspase-3 had no detectable DNA fragmentation. In contrast, when apoptosis was induced by staurosporine, diffuse caspase activation was seen; these MKs had signs of DNA fragmentation, and no proplatelet formation occurred. The pan-caspase inhibitor z-VAD.fmk as well as more specific inhibitors of caspase-3 and caspase-9 blocked proplatelet formation, whereas an inhibitor of calpeptin had no effect. Overexpression of Bcl-2 also inhibited proplatelet formation in maturing MKs. Thus, localized caspase activation is causal to proplatelet formation. We conclude that proplatelet formation is regulated by a caspase activation limited to only some cellular compartments.     

A Randomized Controlled Study of a Group Intervention Program to Enhance Mental Health of Children of Illegal Migrant Workers

Background

The social–ecological environment of undocumented children of migrant workers includes varying levels of risk factors. Growing up in these conditions compromises children’s development on all levels. Many of these children are in need of psychotherapy, however, due to limited resources, only a few of them receive mental health aid.

Objective

The present research undertook to construct and examine the effectiveness of a specialized group intervention program to enhance children’s self-efficacy and mental health.

Methods

Participants were 70 children aged 8–12 of illegal migrant workers in Israel. The repeated measures design included completion of a self-efficacy scale and emotional, behavioral and social difficulties child-report and teacher-report measures. Children were randomly allocated to either an intervention or control group.

Results

The first hypotheses predicting a greater improvement in self-efficacy between the pre-test and post-test for children in the intervention as opposed to control group was confirmed. The second hypothesis predicting a greater reduction in the self- and teacher-reports of emotional, social and behavioral difficulties was confirmed. The third hypothesis predicting a moderating relation between self-efficacy, group type and time on the dependent variables was confirmed only for children’s self-report of their difficulties.

Conclusions

Findings provide evidence for the effectiveness of this short term playful intervention program for this group of disadvantaged children, suggesting its application to other at-risk groups of children.     

Understanding Utilization of Outpatient Clinics for Children with Special Health Care Needs in Southern Israel

To understand the pattern of utilization of ambulatory care by parents of children with special health care needs (CSHCN) and to explore parental challenges in coping with health maintenance of their infants after discharge from a neonatal intensive care unit (NICU). CSHCN require frequent utilization of outpatient ambulatory clinics especially in their first years of life. Multiple barriers are faced by families in disadvantaged populations which might affect adherence to medical referrals. Our study attempts to go beyond quantitative assessment of adherence rates, and capture the influence of parental agency as a critical factor ensuring optimal utilization of healthcare for CSHCN. A prospective, mixed-methods, cohort study followed 158 Jewish and Bedouin-Arab infants in the first year post discharge from NICU in southern Israel. Rates of utilization of ambulatory clinics were obtained from medical records, and quantitative assessment of factors affecting it was based on structured interviews with parents at baseline. Qualitative analysis was based on home visits or telephone in-depth interviews conducted about 1 year post-discharge, to obtain a rich, multilayered, experiential perspectives and explained perceptions by parents. Adherence to post-discharge referrals was generally good, but environmental, cultural, and financial obstacles to healthcare, magnified by communication barriers, forced parents with limited resources to make difficult choices affecting utilization of healthcare services. Improving concordance between primary caregivers and health care providers is crucial, and further development of supportive healthcare for CSHCN in concordance with parental limitations and preferences is needed.     

“Vanishing liver metastases”—A real challenge for liver surgeons

Expanded surgical intervention in colorectal liver metastasis (LM) and improved chemotherapy led to increasing problem of disappearing liver metastases (DLM). Treatment of those continues to evolve and poses a real challenge for HPB surgeons. This review discusses a clinical approach to DLM, emphasizing crucial steps in clinical algorithm. Particular issues such as imaging, intraoperative detection and surgical techniques are addressed. A step-by-step algorithm is suggested.     

Neuroimmunological function in parents of children suffering from cancer

The main aim of this study is to evaluate the relationship between depression and immunological function in parents of children with cancer. Thirty-two parents participated in the study. The parents completed the following assessments: a list of major stressful events in a Hemato-Oncology ward, beck depression inventory II (BDI-II), posttraumatic diagnostic scale (PDS) and quality of life (QOL) questionnaire. A single blood sample was drawn from parents for evaluation of cortisol levels and lymphocyte cell subgroups. The parents were divided into two groups: Those who suffered from depression as defined by BDI-II cutoff score of 14 (depressed parents (DP), n = 7), and non-depressed parents (non-DP, n = 25). In parents of children with cancer the DP group had statistically significantly higher stressful event scores, dysfunction scores (from the PDS) and CD8 percentage compared to the non-DP group. QOL, CD4 percentage and CD4/CD8 ratio were significantly lower in the DP group. The BDI scores significantly positively correlated with events and dysfunctional scores, and significantly negatively correlated with QOL scores and CD4/CD8 ratio. High psychiatric morbidity was found in parents of children with cancer. The findings of altered immunity in DP provide further evidence that the physiological response to stress and depression may alter immune functions.     

Effects of serum and plasma matrices on multiplex immunoassays

Multiplexed fluorescence or electrochemiluminescence immunoassays of soluble cytokines are commonly performed in the context of human serum or plasma, to look for disease biomarkers and to monitor the immune system in a simple and minimally invasive way. These assays provide challenges due to the complexities of the matrix (serum or plasma) and the presence of many cytokines near the limit of detection of the assay. Here, we compare the readout of matched serum and plasma samples, which are generally correlated. However, a subset of cytokines usually have higher levels in serum, and the non-specific background is significantly increased in serum versus plasma. Presumably as a result of this non-specific background, disease-related decreases in low-abundance cytokines can sometimes be detected in plasma but not in serum. We further show, through spike recovery experiments, that both serum and plasma inhibit the readout of many cytokines, with some variability between donors, but with serum causing greater inhibition than plasma in many cases. Standard diluents from different vendors can partially reverse this inhibition to varying degrees. Dilution of samples can also partly overcome the inhibitory effect of the matrix. We also show that dilution is nonlinear and differentially affects various cytokines. Together, these data argue that (1) plasma is a more sensitive matrix for detecting changes in certain low-abundance cytokines; (2) calculation of concentrations in serum or plasma matrices is inherently inaccurate; and (3) dilution of samples should not be assumed to be linear, i.e., all comparisons need to be made among similarly diluted samples.